제 8 장 성염색체성 유전

* 여성은 두개의 X 염색체를 갖고 있다. 그 중 하나는 불활성화됨

* 따라서 여성은 실제 mosaic 이라고 볼 수 있다

* 남성은 한 개의 X 염색체를 갖고 있다.

* 따라서 남성의 경우 돌연변이 된 X 는 항상 표현형으로 나타난다.

* 감수분열시 X 와 Y는 제한적으로 짝짓기를 함(짧은 팔 쪽). 이 부위(상동성부위)와 Yp의 성결정인자사이에서 교차가 발생할 수 있으며, 짧은팔의 끝 쪽 부위의 유전자들은 50%의 교차를 보이므로 상염색체성 유전처럼 보인다.

* 그 외의 유전자들은 X와 Y에서 다르게 존재하므로 성에 따라 특징적인 유전을 나타낸다.

* 성염색체성 유전은 우성 열성에 따라서 그 유전 양상이 다르다.(Table 8.1)

8.1 Y-연관 유전(Holanadric inheritance)

* TDF

* 인간의 Y 연관 질병유전은 알려진 것이 거의 없다.

8.2 X-연관 열성 유전

* 심각한 유전병인 Duchenne muscular dystrophy (DMD)(뒤시엔느 근위축증)은 X-연관 열성 유전으로서 근육이 약해지며 혈중 creatine kinase 농도가 올라감

* 유년기에 발병하여 20세 이전에 사망

* 병의 심한 정도가 일정함

* 보인자는 정상

* 성에 따른 발병비률이 다름

* knight'move pedigree pattern을 보임(Fig. 8.1)

Duchenne muscular dystrophy

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Duchenne muscular dystrophy is an inherited disorder that involves muscle weakness, which quickly gets worse.

Causes

Duchenne muscular dystrophy is a form of muscular dystrophy that worsens quickly. Other muscular dystrophies (including Becker's muscular dystrophy) get worse much more slowly.

Duchenne muscular dystrophy is caused by a defective gene for dystrophin (a protein in the muscles). However, it often occurs in people without a known family history of the condition.

Because of the way the disease is inherited, boys are affected, not girls. The sons of females who are carriers of the disease (women with a defective gene but no symptoms themselves) each have a 50% chance of having the disease. The daughters each have a 50% chance of being carriers.

Duchenne muscular dystrophy occurs in about 1 out of every 3,600 male infants. Because this is an inherited disorder, risks include a family history of Duchenne muscular dystrophy.

Symptoms

Symptoms usually appear before age 6 and may appear as early as infancy. They may include:

Fatigue

Learning difficulties (the IQ can be below 75)

Intellectual disability (possible, but does not get worse over time)

Muscle weakness

Begins in the legs and pelvis, but also occurs less severely in the arms, neck, and other areas of the body

Difficulty with motor skills (running, hopping, jumping)

Frequent falls

Trouble getting up from a lying position or climbing stairs

Weakness quickly gets worse

Progressive difficulty walking

Ability to walk may be lost by age 12, and the child will have to use a wheelchair

Breathing difficulties and heart disease usually start by age 20

Exams and Tests

A complete nervous system (neurological), heart, lung, and muscle exam may show:

Abnormal heart muscle (cardiomyopathy)

Congestive heart failure or irregular heart rhythm (arrhythmias) -- rare

Deformities of the chest and back (scoliosis)

Enlarged muscles of the calves, buttocks, and shoulders (around age 4 or 5). These muscles are eventually replaced by fat and connective tissue (pseudohypertrophy).

Loss of muscle mass (wasting)

Muscle contractures in the heels, legs

Muscle deformities

Respiratory disorders, including pneumonia and poor swallowing, with food or fluid passing into the lungs (in late stages of the disease)

Tests may include:

Electromyography (EMG)

Genetic tests

Muscle biopsy

Serum CPK

Treatment

There is no known cure for Duchenne muscular dystrophy. Treatment aims to control symptoms to improve quality of life.

Steroid drugs can slow the loss of muscle strength. They may be started when the child is diagnosed or when muscle strength begins to decline.

Other treatments include:

Albuteral--a drug used for people with asthma

Amino acids

Carnitine

Coenzyme Q10

Creatine

Fish oil

Green tea extracts

Vitamin E

However, the effects of these treatments have not been proven. Stem cells and gene therapy may be used in the future.

Activity is encouraged. Inactivity (such as bedrest) can make the muscle disease worse. Physical therapy may be helpful to maintain muscle strength and function. Speech therapy is often needed.

Other treatments may include:

Assisted ventilation (used during the day or night)

Drugs to help heart function, such as angiotensin-converting-enzyme inhibitors, beta-blockers, and diuretics

Orthopedic appliances (such as braces and wheelchairs) to improve mobility

Proton pump inhibitors (for people with gastroesophageal reflux)

Several new treatments are being studied in trials.

Support Groups

You can ease the stress of illness by joining a support group where members share common experiences and problems. See muscular dystrophy - support group. The Muscular Dystrophy Association is an excellent source of information on this disease.

Outlook (Prognosis)

Duchenne muscular dystrophy leads to quickly worsening disability. Death usually occurs by age 25, typically from lung disorders.

Possible Complications

Cardiomyopathy

Congestive heart failure (rare)

Deformities

Heart arrhythmias (rare)

Mental impairment (varies, usually minimal)

Permanent, progressive disability

Decreased mobility

Decreased ability to care for self

Pneumonia or other respiratory infections

Respiratory failure

When to Contact a Medical Professional

Call your health care provider if:

Your child has symptoms of Duchenne muscular dystrophy

Symptoms worsen, or new symptoms develop, particularly fever with cough or breathing difficulties

Prevention

Genetic counseling is advised if there is a family history of the disorder. Duchenne muscular dystrophy can be detected with about 95% accuracy by genetic studies performed during pregnancy.

Alternative Names

Pseudohypertrophic muscular dystrophy; Muscular dystrophy - Duchenne type

References

Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Muscular dystrophies. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa:Saunders Elsevier; 2007:chap 608.

출처: http://www.nlm.nih.gov/medlineplus/ency/article/000705.htm

* 보인자 여성과 정상 남자 사이의 발병 확률(Fig.8.2)

* 보인자는 임상적으로 정상이나 lyonization에 의해,  serum creatine 농도가 정상인보다 높은 경향이 있다(보인자의 2/3가 정상인의 최고치 보다 높다)-보인자 탐색에 도움이 됨(Fig8.3)

* 그 외 DNA 분석을 사용하여 진단.

* 보인자일 확률은 가계도, CK 농도등을 이용하여 Bayes's theorem을 사용할 수도 있다(Appendix 2).

* 유전이 아닌 새로운 돌연변이에 의해 발생할 수도 있다(Fig. 8.4).

* 가끔 여성이 이 질환에 걸릴 수도 있음: atypical lyonization(대부분의 근육세포에서 정상 X 염색체가 불활성화, 일란성 쌍둥이 중 한사람만 걸릴 수도 있음). 이 경우 증상은 질병인 남자 보다 약함.

* 이론적으로 보인자의 다른 X 염색체의 돌연변이로 인하여 여성에게 발병할 수 도 있지만 그 경우 증상은 질병인 남자의 경우와 같이 심할 것이다.

* Turner 증후군(mutant X를 불활성화 할 수 없음)의 경우 보인자의  증상은 질병인 남자와 같이 심함.

* X-autosome translocation(Fig 8.5, 정상 X 가 우선적으로 불활성화).

* Becker muscular dystrophy: 증상이 좀 덜함, 돌연변이형태가 다름(유전자는 동일)

* muscular dystrophy에도 상염색체성 우성 및 열성 유전이 있다(genetic heterogeneity)

Becker's muscular dystrophy

Becker muscular dystrophy (also known as Benign pseudohypertrophic muscular dystrophy) is an X-linked recessive inherited disorder characterized by slowly progressive muscle weakness of the legs and pelvis.

It is a type of dystrophinopathy, which includes a spectrum of muscle diseases in which there is insufficient dystrophin produced in the muscle cells, resulting in instability in the structure of muscle cell membrane. This is caused by mutations in the dystrophin gene, which encodes the protein dystrophin. Becker muscular dystrophy is related to Duchenne muscular dystrophy in that both result from a mutation in the dystrophin gene, but in Duchenne muscular dystrophy no functional dystrophin is produced making DMD much more severe than BMD.

Contents

[hide]

1 Eponym

2 Genetics

3 Symptoms

4 Signs and tests

5 Treatment

6 Prognosis

7 Quality of Life

8 Complications

9 References

10 Events

11 External links

[edit] Eponym

Becker Muscular Dystrophy is named after the German doctor Peter Emil Becker (November 23, 1908 Hamburg, Germany - 2000).[1][2][3]

[edit] Genetics

The disorder is inherited with an X-linked recessive inheritance pattern. The gene is located on the X chromosome. Since women have two X chromosomes, if one X chromosome has the non-working gene, the second X chromosome will have a working copy of the gene to compensate. Because of this ability to compensate, women rarely develop symptoms. However, they may do so due to mosaicism. For example, carrier females of mutations are at increased risk for dilated cardiomyopathy. Since men have an X and a Y chromosome and because they don't have another X to compensate for the defective gene, they will develop symptoms if they inherit the non-working gene.

All dystrophinopathies are inherited in an X-linked recessive manner. The risk to the siblings of an affected individual depends upon the carrier status of the mother. Carrier females have a 50% chance of passing the DMD mutation in each pregnancy. Sons who inherit the mutation will be affected; daughters who inherit the mutation will be carriers. Men who have Becker muscular dystrophy can have children, and all their daughters are carriers, but none of the sons will inherit their father's mutation. Prenatal testing through amniocentesis or chorionic villus sampling (CVS) for pregnancies at risk is possible if the DMD mutation is found in a family member or if informative linked markers have been identified. A significant number of Becker muscular dystrophy mutations are spontaneous and are not inherited from a parent.

Becker muscular dystrophy occurs in approximately 3 to 6 in 100,000 male births, making it much less common than Duchenne muscular dystrophy. Symptoms usually appear in men at about ages 8–25, but may sometimes begin later. Patients can lose the ability to walk as early as age 15 in the very rare severe form.

Genetic counseling may be advisable when potential carriers or patients want to have children. Sons of a man with Becker muscular dystrophy do not develop the disorder, but daughters will be carriers (and some carriers can experience some symptoms of muscular dystrophy). The daughters' sons may develop the disorder.

[edit] Symptoms

Muscle weakness, slowly progressive (Difficulty running, hopping, jumping; difficulty walking. However, ability to walk may or may not continue well into adulthood

Toe-walking (walking on toes; also known as equinus)

Use of Gower's Maneuver or a modified form of Gower's Maneuver to get up from floor.

Frequent falls

Difficulty breathing

Skeletal deformities, chest and back (scoliosis)

Muscle deformities (contractions of heels, legs; Pseudohypertrophy of calf muscles)

Fatigue

Heart disease, particularly dilated cardiomyopathy

Elevated CPK (creatine phosphokinase) levels in blood: Elevated CPK levels are more common at younger ages and decreases later in life, perhaps because muscle degeneration occurs more rapidly at younger ages, when there is also more muscle mass to deteriorate.

People with this disorder typically experience progressive muscle weakness of the leg and pelvis muscles, which is associated with a loss of muscle mass (wasting). Muscle weakness also occurs in the arms, neck, and other areas, but not as noticeably severe as in the lower half of the body.

Calf muscles initially enlarge during the ages of 5-15 (an attempt by the body to compensate for loss of muscle strength), but the enlarged muscle tissue is eventually replaced by fat and connective tissue (pseudohypertrophy) as the legs become less used (use of wheelchair).

Muscle contractions, which may be painful, occur in the legs and heels, causing inability to use the muscles because of shortening of muscle fibers and fibrosis of connective tissue. Bones may develop abnormally, causing skeletal deformities of the chest and other areas.

Cardiomyopathy (damage to the heart) does not occur as commonly with this disorder as it does with Duchenne's muscular dystrophy.

[edit] Signs and tests

The pattern of symptom development resembles that of Duchenne muscular dystrophy, but with a later, and much slower rate of progression. Noticeable signs of Muscular Dystrophy also include the lack of pectoral and upper arm muscles, especially when the disease is unnoticed through the early teen years (some men are not diagnosed with BMD until they are in their thirties). Muscle wasting begins in the legs and pelvis (or core), then progresses to the muscles of the shoulders and neck, followed by loss of arm muscles and respiratory muscles. Calf muscle enlargement (pseudohypertrophy) is quite obvious. Cardiomyopathy may occur, but the development of congestive heart failure or arrhythmias (irregular heartbeats) is rare.

Loss of ambulation (loss of ability to walk) may not occur until the person is in his fifties.

Creatine kinase (CPK) levels may be elevated.

An electromyography (EMG) shows that weakness is caused by destruction of muscle tissue rather than by damage to nerves.

Genetic testing

A muscle biopsy (immunohistochemistry or immunoblotting) or genetic test (blood test) confirms the diagnosis.

[edit] Treatment

There is no known cure for Becker muscular dystrophy. Treatment is aimed at control of symptoms to maximize the quality of life.

Activity is encouraged. Inactivity (such as bed rest) or sitting down for too long on plane or car rides can worsen the muscle disease. Physical therapy may be helpful to maintain muscle strength. Orthopedic appliances such as braces and wheelchairs may improve mobility and self-care.

Immunosuppressant steroids like Prednisone have been known to help slow the progression of Becker Muscular Dystrophy. The drug contributes to an increased production of the protein Utrophin which closely resembles Dystrophin, the protein that is defective in BMD. IVIG has proved better in the long term, but its price is a limiting factor.

A Utrophin up-regulation drug by UK Company SummitPLC for Duchenne muscular dystrophy (DMD) is expected to enter clinical trials 2012. This drug could also be used for BMD.

A hepatitis C drug, "Debio-025", that has proven safe for use in Europe shows much promise for halting the muscle necrosis seen in the disease. The investigational drug Debio-025 is a known inhibitor of the protein cyclophilin D, which regulates the swelling of mitochondria in response to cellular injury. Researchers decided to test the drug in mice engineered to carry MD after earlier laboratory tests showed deleting a gene that encodes cycolphilin D reduced swelling and reversed or prevented the disease’s muscle-damaging characteristics. The mice were engineered as models of Duchenne muscular dystrophy and forms caused by a deficiency of two structural proteins, delta-sarcoglycan and laminin alpha2. Treatment with Debio-025 was reported to reduce mitochondrial swelling and necrotic manifestations in mice with muscular dystrophy. Debio-025 has passed Phase II clinical trials in Europe.[citation needed]

During the onset of muscular dystrophy, the loss of certain proteins critical to muscle function – such as dystrophin – can lead to contraction-related micro-tears in muscle fibers and an influx of calcium around muscle tissue. When this happens, cyclophilin D is instructed to make the membranes of mitochondria more permeable. This causes mitochondria to be flooded by calcium and reorganize, swell and eventually rupture. This triggers cell death in muscle fibers and leads to the progressive muscle weakness, wasting and often early death associated with muscular dystrophy. There is another way of slowing down the symptoms or altogether stopping them. Stem Cell Treatment has come a long way in providing treatments for various medical conditions including BMD. In 2009 stem cells from a Placental source were being placed in the human body by incisions and injections, most of the time with amazing results which may or may not be long term.These treatments all took place outside of North America. In 2011, the new method of using your own fatty cells and extracting and treating the stem cells found in your fatty cells and introducing them back into the body with intravenous and as well there clinics in the US specializing in this type of stem cell.

[edit] Prognosis

The progression of Becker muscular dystrophy is highly variable—much more so than Duchenne muscular dystrophy. There is also a form that may be considered as an intermediate between Duchenne and Becker MD (mild DMD or severe BMD). Severity of the disease may be indicated by age of patient at the onset of the disease. One study showed that there may be two distinct patterns of progression in Becker muscular dystrophy: one subgroup which experiences its onset at around age 7 to 8 years of age- this group typically has more cardiac involvement and has trouble climbing stairs by age 20; the other subgroup, which has its onset at around age 12, typically has significantly less cardiac involvement and can still easily climb stairs by age 20.[4] The mean age of onset is age 11, with variation from age 2 to 21.[5]

Becker's muscular dystrophy results in slowly progressive disability, and patients eventually use a cane or wheelchair. Death can occur from age 40 but some patients enjoy a nearly normal lifespan.

[edit] Quality of Life

The quality of life for patients with Becker's muscular dystrophy can be impacted by the symptoms of the disorder. But with assistive devices, independence can be maintained. People affected by Becker's muscular dystrophy can still drive, work, own businesses, start families, and maintain active lifestyles. Those affected by the disorder can also still participate in sports for the disabled, such as wheelchair tennis, Power Soccer, and sled hockey.

[edit] Complications

Deformities (particularly kyphosis)

Permanent, progressive disability manifested as decreased mobility or decreased ability to care for self

Mental impairment - However, this is much less common in BMD than it is in DMD.

Cardiomyopathy

Noncompaction Cardiomyopathy

Pneumonia or other respiratory infections

Respiratory failure

[edit] References

^ synd/915 at Who Named It?

^ Becker PE, Kiener F (1955). "[A new x-chromosomal muscular dystrophy.]" (in German). Arch Psychiatr Nervenkr Z Gesamte Neurol Psychiatr 193 (4): 427–48. PMID 13249581.

^ Becker PE (1957). "[New results of genetics of muscular dystrophy.]" (in German). Acta Genet Stat Med 7 (2): 303–10. PMID 13469170.

^ Delisa, Joel A; Gans, Bruce M; Walsh, Nicholas E (2005). Physical medicine and rehabilitation: Principles and practice. ISBN 978-0-7817-4130-9. http://books.google.com/books?id=1sWk1GYCvKoC&printsec=frontcover#PPA918,M1.

^

출처:

http://en.wikipedia.org/wiki/Becker's_muscular_dystrophy

8.3 기타 X-연관 열성유전

* 412 가지(Table 8.2)

* 종족에 따른 발생빈도 차이가 있음. 예) 색맹은 에스키모인에게 거의 없다. 또한, 어떤 종종에서는 glucose-6-phsphate dehydrogenase 결핍증이 영국의 색맹만큼 많은 경우도 있다.

Glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase (abbreviated G6PD or G6PDH), a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism. G6PD deficiency is the most common human enzyme defect.[1] Individuals with the disease may exhibit nonimmune hemolytic anemia in response to a number of causes, most commonly infection or exposure to certain medications or chemicals. G6PD deficiency is closely linked to favism, a disorder characterized by a hemolytic reaction to consumption of broad beans, with a name derived from the Italian name of the broad bean (fava). The name favism is sometimes used to refer to the enzyme deficiency as a whole, although this is misleading as not all people with G6PD deficiency will manifest a physically observable reaction to consumption of broad beans.

Contents

[hide]

1 Classification

2 Signs and symptoms

3 Cause

3.1 Environmental triggers

3.2 Genetics

4 Pathophysiology

5 Diagnosis

6 Treatment

7 Epidemiology

8 Prognosis

9 History

10 References

11 External links

[edit] Classification

The World Health Organization classifies G6PD genetic variants into five classes, the first three of which are deficiency states.[2]

Severe deficiency (<10% activity) with chronic (nonspherocytic) hemolytic anemia

Severe deficiency (<10% activity), with intermittent hemolysis

Mild deficiency (10-60% activity), hemolysis with stressors only

Non-deficient variant, no clinical sequelae

Increased enzyme activity, no clinical

[edit] Signs and symptoms

A 4-year old boy diagnosed with glucose-6-phosphate dehydrogenase deficiency showing jaundice in the sclera

Most individuals with G6PD deficiency are asymptomatic.

Symptomatic patients are almost exclusively male, due to the X-linked pattern of inheritance, but female carriers can be clinically affected due to unfavorable lyonization, where random inactivation of an X-chromosome in certain cells creates a population of G6PD-deficient red blood cells coexisting with normal red cells. A typical female with one affected X chromosome will show the deficiency in approximately half of her red blood cells. However, in rare cases, including double X deficiency, the ratio can be much more than half, making the individual almost as sensitive as a male.

Abnormal red blood cell breakdown (hemolysis) in G6PD deficiency can manifest in a number of ways, including the following:

Prolonged neonatal jaundice, possibly leading to kernicterus (arguably the most serious complication of G6PD deficiency)

Hemolytic crises in response to:

Illness (especially infections)

Certain drugs (see below)

Certain foods, most notably broad beans

Certain chemicals

Diabetic ketoacidosis

Very severe crises can cause acute renal failure

Favism may be formally defined as a haemolytic response to the consumption of broad beans. All individuals with favism show G6PD deficiency. However, not all individuals with G6PD deficiency show favism. For example, in a small study of 757 Saudi men, more than 42% showed a variant of G6PD deficiency, but none displayed symptoms of favism.[3] Favism is known to be more prevalent in infants and children, and G6PD genetic variant can influence chemical sensitivity.[citation needed] Other than this, the specifics of the chemical relationship between favism and G6PD are not well understood.

[edit] Cause

[edit] Environmental triggers

Many substances are potentially harmful to people with G6PD deficiency. Variation in response to these substance makes individual predictions difficult. Antimalarial drugs that can cause acute haemolysis in people with G6PD deficiency include primaquine, pamaquine, and chloroquine. There is evidence that other antimalarials may also exacerbate G6PD deficiency, but only at higher doses. Sulfonamides (such as sulfanilamide, sulfamethoxazole, and mafenide), thiazolesulfone, methylene blue, and naphthalene should also be avoided by people with G6PD deficiency, as should certain analgesics (such as aspirin, phenazopyridine, and acetanilide) and a few non-sulfa antibiotics (nalidixic acid, nitrofurantoin, isoniazid, dapsone, and furazolidone).[1][4][5] Henna has been known to cause haemolytic crisis in G6PD-deficient infants.[6]

[edit] Genetics

The two variants (G6PD− and G6PD Mediterranean) cause most clinically significant hemolytic anemias. G6PD− has an occurrence of 10% of American blacks while G6PD Mediterranean is prevalent in the Middle East. These variants are believed to stem from a protective effect against Plasmodium falciparum malaria.[7]

All mutations that cause G6PD deficiency are found on the long arm of the X chromosome, on band Xq28. The G6PD gene spans some 18.5 kilobases.[4] The following variants and mutations are well-known and described:

Table 1. Descriptive mutations and variants
Variants or mutations				Gene			Protein
Designation	Short name	Isoform G6PD-Protein	OMIM-Code	Type	Subtype	Position	Position	Structure change	Function change
G6PD-A(+)	Gd-A(+)	G6PD A	+305900.0001	Polymorphism nucleotide	A→G	376 (Exon 5)	126	Asparagine→Aspartic acid (ASN126ASP)	No enzyme defect (variant)
G6PD-A(-)	Gd-A(-)	G6PD A	+305900.0002	Substitution nucleotide	G→A	376 (Exon 5) and 202	68 and 126	Valine→Methionine (VAL68MET) Asparagine→Aspartic acid (ASN126ASP)
G6PD-Mediterran	Gd-Med	G6PD B	+305900.0006	Substitution nucleotide	C→T	563 (Exon 6)	188	Serine→Phenylalanine (SER188PHE)	Class II
G6PD-Canton	Gd-Canton	G6PD B	+305900.0021	Substitution nucleotide	G→T	1376	459	Arginine→Leucine (ARG459LEU)	Class II
G6PD-Chatham	Gd-Chatham	G6PD	+305900.0003	Substitution nucleotide	G→A	1003	335	Alanine→Threonine (ALA335THR)	Class II
G6PD-Cosenza	Gd-Cosenza	G6PD B	+305900.0059	Substitution nucleotide	G→A	1376	459	Arginine→Proline (ARG459PRO)	G6PD-activity <10%, thus high portion of patients.
G6PD-Mahidol	Gd-Mahidol	G6PD	+305900.0005	Substitution nucleotide	G→A	487 (Exon 6)	163	Glycine→Serine (GLY163SER)	Class II
G6PD-Orissa	Gd-Orissa	G6PD	+305900.0047	Substitution nucleotide			44	Alanine→Glycine (ALA44GLY)	NADP-binding place affected. Higher stability than other variants.
G6PD-Asahi	Gd-Asahi	G6PD A-	+305900.0054	Substitution nucleotide (several)	A→G ± G→A	376 (Exon 5) 202	126 68	Asparagine→Aspartic acid (ASN126ASP) Valine→Methionine (VAL68MET)	Class III.

[edit] Pathophysiology

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway (see image, also known as the HMP shunt pathway). G6PD converts glucose-6-phosphate into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of this metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). The NADPH in turn maintains the supply of reduced glutathione in the cells that is used to mop up free radicals that cause oxidative damage.

The G6PD / NADPH pathway is the only source of reduced glutathione in red blood cells (erythrocytes). The role of red cells as oxygen carriers puts them at substantial risk of damage from oxidizing free radicals except for the protective effect of G6PD/NADPH/glutathione.

People with G6PD deficiency are therefore at risk of hemolytic anemia in states of oxidative stress. Oxidative stress can result from infection and from chemical exposure to medication and certain foods. Broad beans, e.g., fava beans, contain high levels of vicine, divicine, convicine and isouramil, all of which are oxidants.

When all remaining reduced glutathione is consumed, enzymes and other proteins (including hemoglobin) are subsequently damaged by the oxidants, leading to electrolyte imbalance, cross-bonding and protein deposition in the red cell membranes. Damaged red cells are phagocytosed and sequestered (taken out of circulation) in the spleen. The hemoglobin is metabolized to bilirubin (causing jaundice at high concentrations). The red cells rarely disintegrate in the circulation, so hemoglobin is rarely excreted directly by the kidney, but this can occur in severe cases, causing acute renal failure .

Deficiency of G6PD in the alternative pathway causes the build up of glucose and thus there is an increase of advanced glycation endproducts (AGE). The deficiency also causes a reduction of NADPH which is necessary for the formation of Nitric Oxide (NO). The high prevalence of diabetes mellitus type 2 and hypertension in Afro-Caribbeans in the West could be directly related to the incidence of G6PD deficiency in those populations.[8]

Although female carriers can have a mild form of G6PD deficiency (dependent on the degree of inactivation of the unaffected X chromosome – see lyonization), homozygous females have been described; in these females there is co-incidence of a rare immune disorder termed chronic granulomatous disease (CGD).

[edit] Diagnosis

The diagnosis is generally suspected when patients from certain ethnic groups (see epidemiology) develop anemia, jaundice and symptoms of hemolysis after challenges from any of the above causes, especially when there is a positive family history.

Generally, tests will include:

Complete blood count and reticulocyte count; in active G6PD, Heinz bodies can be seen in red blood cells on a blood film;

Liver enzymes (to exclude other causes of jaundice);

Lactate dehydrogenase (elevated in hemolysis and a marker of hemolytic severity)

Haptoglobin (decreased in hemolysis);

A "direct antiglobulin test" (Coombs' test) – this should be negative, as hemolysis in G6PD is not immune-mediated;

When there are sufficient grounds to suspect G6PD, a direct test for G6PD is the "Beutler fluorescent spot test", which has largely replaced an older test (the Motulsky dye-decolouration test). Other possibilities are direct DNA testing and/or sequencing of the G6PD gene.

The Beutler fluorescent spot test is a rapid and inexpensive test that visually identifies NADPH produced by G6PD under ultraviolet light. When the blood spot does not fluoresce, the test is positive; it can be falsely negative in patients who are actively hemolysing. It can therefore only be done 2–3 weeks after a hemolytic episode.

When a macrophage in the spleen identifies a RBC with a Heinz body, it removes the precipitate and a small piece of the membrane, leading to characteristic "bite cells". However, if a large number of Heinz bodies are produced, as in the case of G6PD deficiency, some Heinz bodies will nonetheless be visible when viewing RBCs that have been stained with crystal violet. This easy and inexpensive test can lead to an initial presumption of G6PD deficiency, which can be confirmed with the other tests.

[edit] Treatment

The most important measure is prevention – avoidance of the drugs and foods that cause hemolysis. Vaccination against some common pathogens (e.g. hepatitis A and hepatitis B) may prevent infection-induced attacks.[9]

In the acute phase of hemolysis, blood transfusions might be necessary, or even dialysis in acute renal failure. Blood transfusion is an important symptomatic measure, as the transfused red cells are generally not G6PD deficient and will live a normal lifespan in the recipient's circulation.

Some patients may benefit from removal of the spleen (splenectomy),[10] as this is an important site of red cell destruction. Folic acid should be used in any disorder featuring a high red cell turnover. Although vitamin E and selenium have antioxidant properties, their use does not decrease the severity of G6PD deficiency.

[edit] Epidemiology

G6PDH is the most common human enzyme defect, being present in more than 400 million people worldwide.[11] African, Middle Eastern and South Asian people are affected the most along with those who are mixed with any of the above.[12] A side effect of this disease is that it confers protection against malaria,[13] in particular the form of malaria caused by Plasmodium falciparum, the most deadly form of malaria. A similar relationship exists between malaria and sickle-cell disease. One theory to explain this, is that cells infected with the Plasmodium parasite are cleared more rapidly by the spleen. This phenomenon might give G6PDH deficiency carriers an evolutionary advantage by increasing their fitness in malarial endemic environments.

[edit] Prognosis

G6PD-deficient individuals do not appear to acquire any illnesses more frequently than other people, and may have less risk than other people for acquiring ischemic heart disease and cerebrovascular disease.[14]

[edit] History

Favism is a disorder characterized by hemolytic anemia in response to ingestion of fava beans. Favism as a diagnosis has been known since antiquity. One theory for the Pythagoreans' avoidance of beans is avoidance of favism, but more likely, this was a philosophical matter, such as the belief that beans and humans were created from the same material.[15][16]

The modern understanding of the condition began with the analysis of patients who exhibited sensitivity to primaquine.[17] The discovery of G6PD deficiency relied heavily upon the testing of prisoner volunteers at Illinois State Penitentiary, although today such studies cannot be performed. When some prisoners were given the drug primaquine, some developed hemolytic anemia but others did not. After studying the mechanism through Cr51 testing, it was conclusively shown that the hemolytic effect of primaquine was due to an intrinsic defect of erythrocytes.[18]

[edit] References

^ a b Frank JE (October 2005). "Diagnosis and management of G6PD deficiency". Am Fam Physician 72 (7): 1277–82. PMID 16225031. http://www.aafp.org/afp/20051001/1277.html.

^ Mazza, Joseph (2001). Manual of Clinical Hematology. Lippincott Williams &Wilkins. pp. 101–2. ISBN 0-7817-2980-7.

^ Al-Ali, AK (1996). "Common G6PD variant from Saudi population and its prevalence" (PDF). Annals of Saudi Medicine 16 (6): 654–6. ISSN 02564947. PMID 17429252. http://www.kfshrc.edu.sa/annals/Old/166/95-371.pdf. Retrieved May 17, 2009. "This has led to the identification of one genetically determined common variant, 'G6PD Mediterranean.' The overall prevalence rate of this deficiency in these areas was determined to be in excess of 42%. None of the subjects studied displayed any sign of favism"

^ a b Warrell, David A.; Timothy M. Cox, John D. Firth, Edward J. Benz (2005). Oxford Textbook of Medicine, Volume Three. Oxford University Press. pp. 720–725. ISBN 0-19-857013-9.

^ A comprehensive list of drugs and chemicals that are potentially harmful in G6PD deficiency can be found in Beutler E (December 1994). "G6PD deficiency". Blood 84 (11): 3613–36. PMID 7949118. http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=7949118..

^ Raupp P, Hassan JA, Varughese M, Kristiansson B (2001). "Henna causes life threatening haemolysis in glucose-6-phosphate dehydrogenase deficiency". Arch. Dis. Child. 85 (5): 411–2. doi:10.1136/adc.85.5.411. PMC 1718961. PMID 11668106. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1718961/.

^ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009-05-28). Robbins and Cotran Pathologic Basis of Disease, Professional Edition: Expert Consult - Online (Robbins Pathology) (Kindle Locations 33351-33354). Elsevier Health. Kindle Edition.

^ Gaskin RS, Estwick D, Peddi R (2001). "G6PD deficiency: its role in the high prevalence of hypertension and diabetes mellitus". Ethnicity &disease 11 (4): 749–54. PMID 11763298.

^ Monga A, Makkar RP, Arora A, Mukhopadhyay S, Gupta AK (July 2003). "Case report: Acute hepatitis E infection with coexistent glucose-6-phosphate dehydrogenase deficiency". Can J Infect Dis 14 (4): 230–1. PMC 2094938. PMID 18159462. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2094938/.

^ Hamilton JW, Jones FG, McMullin MF (August 2004). "Glucose-6-phosphate dehydrogenase Guadalajara – a case of chronic non-spherocytic haemolytic anaemia responding to splenectomy and the role of splenectomy in this disorder". Hematology 9 (4): 307–9. doi:10.1080/10245330410001714211. PMID 15621740. http://www.informaworld.com/openurl?genre=article&doi=10.1080/10245330410001714211&magic=pubmed.

^ Cappellini MD, Fiorelli G (January 2008). "Glucose-6-phosphate dehydrogenase deficiency". Lancet 371 (9606): 64–74. doi:10.1016/S0140-6736(08)60073-2. PMID 18177777.

^ G-6-PD FAQ section

^ Mehta A, Mason PJ, Vulliamy TJ (2000). "Glucose-6-phosphate dehydrogenase deficiency". Baillieres Best Pract. Res. Clin. Haematol. 13 (1): 21–38. PMID 10916676.

^ thefreedictionary.com >glucose-6-phosphate dehydrogenase deficiency citing: Gale Encyclopedia of Medicine. Copyright 2008

^ Gabrielle Hatfield, review of Frederick J. Simoons, Plants of Life, Plants of Death, University of Wisconsin Press, 1999. ISBN 0-299-15904-3. In Folklore 111:317–318 (2000). at JSTOR

^ Rendall, Steven; Riedweg, Christoph (2005). Pythagoras: his life, teaching, and influence. Ithaca, N.Y: Cornell University Press. ISBN 0-8014-4240-0.

^ Alving AS, Carson PE, Flanagan CL, Ickes CE (September 1956). "Enzymatic deficiency in primaquine-sensitive erythrocytes" (PDF). Science 124 (3220): 484–5. Bibcode 1956Sci...124..484C. doi:10.1126/science.124.3220.484-a. PMID 13360274. http://www.sciencemag.org/cgi/reprint/124/3220/484-a.

^ Beutler E (January 2008). "Glucose-6-phosphate dehydrogenase deficiency: a historical perspective". Blood 111 (1): 16–24. doi:10.1182/blood-2007-04-077412. PMID 18156501. http://bloodjournal.hematologylibrary.org/cgi/content/full/111/1/16.

출처: http://en.wikipedia.org/wiki/Glucose-6-phosphate_dehydrogenase_deficiency

Red Green Color Blindness

For some people, roses are not red but violets are

still blue. Many people suffer from a type of color blindness called “red green color blindness” and it is just like it sounds - a condition that confuses people’s visions of different shades of red and green. It is the most common form of color blindness and affects six percent of males.

Color blindness is generally inherited but can also be acquired. Different types of inherited defects are broken up into three categories: monochromacy, dichromacy and anomalous trichromacy. Monochromacy is a rare condition that prevents people from seeing any types of shades and forces them to live in world full of gray. Anomalous trichromacy, can be inherited but is more often acquired. This condition makes it difficult for people to detect slightly different shades. Dichromacy is broken into two groups: hereditary Tritanopia which is a blue-yellow defect and protanopia &deuteranopia which means red-green color blindness.

Protanopia and deuteranopia can be inherited from relatives who suffer from missing or incorrect visual pigments. It can also be acquired from aging or eye injuries or other eye problems such as glaucoma, macular degeneration, cataracts or diabetic retinopathy.

Many people live for years before discovering they suffer from red green color blindness. Unless it becomes apparent through outside observers or an optometrist, people may not notice they see different shades of red and green. However, for those who wish to pursue careers in professions such as law enforcement, rail road, military, firefighting and electrical wiring, they may be turned down due to their inability to distinguish between reds and greens.

Pseudoisochromatic plate tests are often used to test color vision. Many industries will test color vision abilities of applicants with these plates before moving them along in the hiring process. These tests will immediately and accurately identify people who suffer from red green color blindness.

Fortunately color blind treatment is available for people ready to see the world for all that its worth. Since 1999, Dr. Thomas Azman has been treating people who suffer from red green color blindness with his ColorCorrection System™. The system is able to change the wave lengths of each color going into one or both eyes using eyeglasses or soft contact lenses. Dr. Azman has an astonishing 100 percent success rate with helping color blind people pass many types of pseudoisochromatic plate tests.

The ColorCorrection System™ has defeated the notion that no color blind treatment exists and has helped people open their eyes to a new world full different shades of reds and greens.

출처: http://www.colormax.org/red-green-color-blindness.htm

• Reverse color blindness test
Color vision deficient people have a tendency to better night vision and, in some situations, they can perceive variations in luminosity that color-sighted people could not. In fact, most color blind people can easily read what is written in the picture below... That means, if you fail the test, you probably have the full range of color sensitivity that is attributed to color-sighted people. Anyway, this test is not to be considered by itself sufficient to determinate defective color vision.
(Highlight answer: NO)

Image taken from Sarcone's book Puzzillusions

Color blindness

From Wikipedia, the free encyclopedia

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This article is about color blindness in humans. For color blindness in other species, see Color vision.

"Colorblind" and "Colourblind" redirect here. For other uses, see Colorblind (disambiguation).

Color blindness or color deficiency
Classification and external resources
An 1895 illustration of normal vision and various kinds of color blindness
ICD-10	H53.5
ICD-9	368.5
DiseasesDB	2999
MedlinePlus	001002
MeSH	D003117

Color blindness or color vision deficiency is the inability or decreased ability to see color, or perceive color differences, under normal lighting conditions. Color blindness affects a significant percentage of the population.[1] There is no actual blindness but there is a deficiency of color vision. The most usual cause is a fault in the development of one or more sets of retinal cones that perceive color in light and transmit that information to the optic nerve. This type of color blindness is usually a sex-linked condition. The genes that produce photopigments are carried on the X chromosome; if some of these genes are missing or damaged, color blindness will be expressed in males with a higher probability than in females because males only have one X chromosome (in females, a functional gene on only one of the two X chromosomes is sufficient to yield the needed photopigments).[2]

Color blindness can also be produced by physical or chemical damage to the eye, the optic nerve, or parts of the brain. For example, people with achromatopsia suffer from a completely different disorder, but are nevertheless unable to see colors.

The English chemist John Dalton published the first scientific paper on this subject in 1798, "Extraordinary facts relating to the vision of colours",[3] after the realization of his own color blindness. Because of Dalton's work, the general condition has been called daltonism, although in English this term is now used more narrowly for deuteranopia alone.

Color blindness is usually classed as a mild disability, but there are occasional circumstances where it can give an advantage. Some studies conclude that color blind people are better at penetrating certain color camouflages. Such findings may give an evolutionary reason for the high prevalence of red–green color blindness.[4] And there is also a study suggesting that people with some types of color blindness can distinguish colors that people with normal color vision are not able to distinguish. [5]

Contents

1 Background

2 Classification

2.1 By cause

2.2 By clinical appearance

3 Causes

3.1 Evolutionary arguments

3.2 Genetics

3.3 Other causes

3.4 Types

3.5 Congenital

3.5.1 Monochromacy

3.5.2 Dichromacy

3.5.3 Anomalous trichromacy

3.6 Total color blindness

3.7 Red–green color blindness

3.8 Blue–yellow color blindness

4 Diagnosis

5 Management

6 Epidemiology

7 Society and culture

7.1 Design implications of color blindness

7.2 Occupations

7.3 Driving motor vehicles

7.4 Piloting aircraft

7.5 Art

7.6 Rights of people with color blindness

7.6.1 Brazil

8 Problems and compensations

9 See also

10 References

11 Further reading

12 External links

Background

Main article: Trichromatic color vision

Color blindness affects a large number of individuals, with protanopia and deuteranopia being the most common types of color blindness.[6] The typical human retina contains two kinds of light cells: the rod cells (active in low light) and the cone cells (active in normal daylight). Normally, there are three kinds of cones, each containing a different pigment, which are activated when the pigments absorb light. The spectral sensitivities of the cones differ; one is most sensitive to short wavelengths, one to medium wavelengths, and the third to medium-to-long wavelengths within the visible spectrum, with their peak sensitivities in the blue, green, and yellow-green regions of the spectrum, respectively. The absorption spectra of the three systems overlap, and combine to cover the visible spectrum. These receptors are often called S cones, M cones, and L cones, for short, medium, and long wavelength; but they are also often referred to as blue cones, green cones, and red cones, respectively.

Although these receptors are often referred to as "blue, green, and red" receptors, this terminology is inaccurate. The receptors are each responsive to a wide range of wavelengths. For example, the long wavelength, "red", receptor has its peak sensitivity in the yellow-green, some way from the red end (longest wavelength) of the visible spectrum. The sensitivity of normal color vision actually depends on the overlap between the absorption ranges of the three systems: different colors are recognized when the different types of cone are stimulated to different degrees. Red light, for example, stimulates the long wavelength cones much more than either of the others, and reducing the wavelength causes the other two cone systems to be increasingly stimulated, causing a gradual change in hue.

Many of the genes involved in color vision are on the X chromosome, making color blindness much more common in males than in females because males have only one X chromosome, while females have two. Because this is an X-linked trait an estimated 2-3% of women have a 4th color cone[citation needed] and can be considered tetrachromats although it is not clear that this provides an advantage in color discrimination.

Classification

By cause

A rainbow of colors as viewed by a person with no color vision deficiencies.

The same rainbow as viewed by a person with protanopia.

The same rainbow as viewed by a person with deuteranopia.

The same rainbow as viewed by a person with tritanopia.

Color vision deficiencies can be classified as acquired or inherited.

Acquired

Inherited: There are three types of inherited or congenital color vision deficiencies: monochromacy, dichromacy, and anomalous trichromacy.

Monochromacy, also known as "total color blindness," is the lack of ability to distinguish colors (and thus the person views everything as if it were on a black and white television); caused by cone defect or absence. Monochromacy occurs when two or all three of the cone pigments are missing and color and lightness vision is reduced to one dimension.

Rod monochromacy (achromatopsia) is an exceedingly rare, nonprogressive inability to distinguish any colors as a result of absent or nonfunctioning retinal cones. It is associated with light sensitivity (photophobia), involuntary eye oscillations (nystagmus), and poor vision.

Cone monochromacy is a rare total color blindness that is accompanied by relatively normal vision, electroretinogram, and electrooculogram. Cone monochromacy can also be a result of having more than one type of dichromatic color blindness. People who have, for instance, both protanopia and tritanopia are considered to have cone monochromacy. Since cone monochromacy is the lack of/damage of more than one cone in retinal environment, having two types of dichromacy would be an equivalent.

Dichromacy is a moderately severe color vision defect in which one of the three basic color mechanisms is absent or not functioning. It is hereditary and, in the case of Protanopia or Deuteranopia, sex-linked, affecting predominantly males. Dichromacy occurs when one of the cone pigments is missing and color is reduced to two dimensions.

Protanopia is a severe type of color vision deficiency caused by the complete absence of red retinal photoreceptors. It is a form of dichromatism in which red appears black and therefore human can see light only from 400 nm to 650 nm. It is hereditary, sex-linked, and present in 1% of males.

Deuteranopia is a color vision deficiency in which the green retinal photoreceptors are absent, moderately affecting red–green hue discrimination. It is a form of dichromatism in which there are only two cone pigments present. It is likewise hereditary and sex-linked.

Tritanopia is a very rare color vision disturbance in which there are only two cone pigments present and a total absence of blue retinal receptors. It is related to Chromosome "7".

Anomalous trichromacy is a common type of inherited color vision deficiency, occurring when one of the three cone pigments is altered in its spectral sensitivity. This results in an impairment, rather than loss, of trichromacy (normal three-dimensional color vision).

Protanomaly is a mild color vision defect in which an altered spectral sensitivity of red retinal receptors (closer to green receptor response) results in poor red–green hue discrimination. It is hereditary, sex-linked, and present in 1% of males.

Deuteranomaly, caused by a similar shift in the green retinal receptors, is by far the most common type of color vision deficiency, mildly affecting red–green hue discrimination in 5% of European males. It is hereditary and sex-linked.

Tritanomaly is a rare, hereditary color vision deficiency affecting blue–yellow hue discrimination. Unlike most other forms, it is not sex-linked, it is related to Chromosome "7".[7]

By clinical appearance

Based on clinical appearance, color blindness may be described as total or partial. Total color blindness is much less common than partial color blindness.[8] There are two major types of color blindness: those who have difficulty distinguishing between red and green, and who have difficulty distinguishing between blue and yellow.[9][10]

Total color blindness

Partial color blindness

Red–green

Dichromacy (protanopia and deuteranopia)

Anomalous trichromacy (protanomaly and deuteranomaly)

Blue–yellow

Dichromacy (tritanopia)

Anomalous trichromacy (tritanomaly)

Causes

Evolutionary arguments

Any recessive genetic characteristic that persists at a level as high as 5% is generally regarded as having some sort of evolutionary advantage over the long term, such as better discrimination of color camouflaged objects especially in low-light conditions.[4][11] At one time the U.S. Army found that color blind people could spot "camouflage" colors that fooled those with normal color vision.[12] Humans have a higher percentage of color blindness than macaque monkeys according to recent research.[13] It is worth noting, however, that the effect is frequency dependent, because, if the majority of people were dichromats, camouflage dyes would be selected on the basis of deceiving dichromats instead.

Another possible advantage might result from the presence of a tetrachromic female. Owing to X-chromosome inactivation, females who are heterozygous for anomalous trichromacy ought to have at least four types of cone in their retinae. It is possible that this affords them an extra dimension of color vision, by analogy to New World monkeys where heterozygous females gain trichromacy in a basically dichromatic species.[14][15]

Genetics

Color blindness can be inherited. It is most commonly inherited from mutations on the X chromosome but the mapping of the human genome has shown there are many causative mutations – mutations capable of causing color blindness originate from at least 19 different chromosomes and 56 different genes (as shown online at the Online Mendelian Inheritance in Man (OMIM) database at Johns Hopkins University). Two of the most common inherited forms of color blindness are protanopia, and deuteranopia.[16] One of the common color vision defects is the red-green deficiency which is present in about 8 percent of males and 0.5 percent of females of Northern European ancestry.[17]

Some of the inherited diseases known to cause color blindness are:

cone dystrophy

cone-rod dystrophy

achromatopsia (aka rod monochromatism, aka stationary cone dystrophy, aka cone dysfunction syndrome)

blue cone monochromatism,

Leber's congenital amaurosis.

retinitis pigmentosa (initially affects rods but can later progress to cones and therefore color blindness).

Inherited color blindness can be congenital (from birth), or it can commence in childhood or adulthood. Depending on the mutation, it can be stationary, that is, remain the same throughout a person's lifetime, or progressive. As progressive phenotypes involve deterioration of the retina and other parts of the eye, certain forms of color blindness can progress to legal blindness, i.e., an acuity of 6/60 or worse, and often leave a person with complete blindness.

Color blindness always pertains to the cone photoreceptors in retinas, as the cones are capable of detecting the color frequencies of light.

About 8 percent of males, but only 0.5 percent of females, are color blind in some way or another, whether it is one color, a color combination, or another mutation.[18] The reason males are at a greater risk of inheriting an X linked mutation is that males only have one X chromosome (XY, with the Y chromosome carrying altogether different genes than the X chromosome), and females have two (XX); if a woman inherits a normal X chromosome in addition to the one that carries the mutation, she will not display the mutation. Men do not have a second X chromosome to override the chromosome that carries the mutation. If 5% of variants of a given gene are defective, the probability of a single copy being defective is 5%, but the probability that two copies are both defective is 0.05 × 0.05 = 0.0025, or just 0.25%.

Other causes

Other causes of color blindness include brain or retinal damage caused by shaken baby syndrome, accidents and other trauma which produce swelling of the brain in the occipital lobe, and damage to the retina caused by exposure to ultraviolet light (10 nm - 300 nm). Damage often presents itself later on in life.

Color blindness may also present itself in the spectrum of degenerative diseases of the eye, such as age-related macular degeneration, and as part of the retinal damage caused by diabetes. Another factor that may affect color blindness includes a deficiency in Vitamin A.[19]

Types

The different kinds of inherited color blindness result from partial or complete loss of function of one or more of the different cone systems. When one cone system is compromised, dichromacy results. The most frequent forms of human color blindness result from problems with either the middle or long wavelength sensitive cone systems, and involve difficulties in discriminating reds, yellows, and greens from one another. They are collectively referred to as "red–green color blindness", though the term is an over-simplification and is somewhat misleading. Other forms of color blindness are much more rare. They include problems in discriminating blues from yellows, and the rarest forms of all, complete color blindness or monochromacy, where one cannot distinguish any color from grey, as in a black-and-white movie or photograph.

Congenital

Congenital color vision deficiencies are subdivided based on the number of primary hues needed to match a given sample in the visible spectrum.

Monochromacy

Monochromacy is the condition of possessing only a single channel for conveying information about color. Monochromats possess a complete inability to distinguish any colors and perceive only variations in brightness. It occurs in two primary forms:

Rod monochromacy, frequently called achromatopsia, where the retina contains no cone cells, so that in addition to the absence of color discrimination, vision in lights of normal intensity is difficult. While normally rare, achromatopsia is very common on the island of Pingelap, a part of the Pohnpei state, Federated States of Micronesia, where it is called maskun: about 10% of the population there has it, and 30% are unaffected carriers. The island was devastated by a storm in the 18th century, and one of the few male survivors carried a gene for achromatopsia; the population grew to several thousand before foreign troops introduced diseases to the island in the 1940s; the population of the island is now approximately 250.

Cone monochromacy is the condition of having both rods and cones, but only a single kind of cone. A cone monochromat can have good pattern vision at normal daylight levels, but will not be able to distinguish hues. Blue cone monochromacy (X chromosome) is caused by a complete absence of L and M cones (red and green). It is encoded at the same place as red–green color blindness on the X chromosome. Peak spectral sensitivities are in the blue region of the visible spectrum (near 440 nm). People with this condition generally show nystagmus ("jiggling eyes"), photophobia (light sensitivity), reduced visual acuity, and myopia (nearsightedness).[20] Visual acuity usually falls to the 20/50 to 20/400 range.

Dichromacy

Protanopes, deuteranopes, and tritanopes are dichromats; that is, they can match any color they see with some mixture of just two primary colors (whereas normally humans are trichromats and require three primary colors). These individuals normally know they have a color vision problem and it can affect their lives on a daily basis. Two percent of the male population exhibit severe difficulties distinguishing between red, orange, yellow, and green. A certain pair of colors, that seem very different to a normal viewer, appear to be the same color (or different shades of same color) for a such dichromat. The terms protanopia, deuteranopia, and tritanopia come from Greek and literally mean "inability to see (anopia) with the first (prot-), second (deuter-), or third (trit-) [cone]", respectively.

Test for protanopia[Note 1]
This image contains the number 37, but someone who is protanopic may not be able to see it.

Protanopia (1% of males): Lacking the long-wavelength sensitive retinal cones, those with this condition are unable to distinguish between colors in the green–yellow–red section of the spectrum. They have a neutral point at a cyan-like wavelength around 492 nm (see spectral color for comparison) – that is, they cannot discriminate light of this wavelength from white. For a protanope, the brightness of red, orange, and yellow are much reduced compared to normal. This dimming can be so pronounced that reds may be confused with black or dark gray, and red traffic lights may appear to be extinguished. They may learn to distinguish reds from yellows primarily on the basis of their apparent brightness or lightness, not on any perceptible hue difference. Violet, lavender, and purple are indistinguishable from various shades of blue because their reddish components are so dimmed as to be invisible. For example, pink flowers, reflecting both red light and blue light, may appear just blue to the protanope. Very few people have been found who have one normal eye and one protanopic eye. These unilateral dichromats report that with only their protanopic eye open, they see wavelengths shorter than neutral point as blue and those longer than it as yellow. This is a rare form of color blindness.

Test for deuteranopia[Note 1]
This image shows a number 49, but someone who is deuteranopic may not be able to see it.

Deuteranopia (1% of males): Lacking the medium-wavelength cones, those affected are again unable to distinguish between colors in the green–yellow–red section of the spectrum. Their neutral point is at a slightly longer wavelength, 498 nm, a more greenish hue of cyan. A deuteranope suffers the same hue discrimination problems as protanopes, but without the abnormal dimming. Purple colors are not perceived as something opposite to spectral colors; all these appear similarly. This form of colorblindness is also known as Daltonism after John Dalton. (Dalton's diagnosis was confirmed as deuteranopia in 1995, some 150 years after his death, by DNA analysis of his preserved eyeball.) Deuteranopic unilateral dichromats report that with only their deuteranopic eye open, they see wavelengths shorter than neutral point as blue and longer than it as yellow.[21]

Test for tritanopia[Note 1]
This image shows the number 56, but someone who is tritanopic may not be able to see it.

Tritanopia (less than 1% of males and females): Lacking the short-wavelength cones, those affected see short-wavelength colors (blue, indigo and a spectral violet) drastically dimmed, some of these colors even as black. Yellow is indistinguishable from white, and purple colors are perceived as various shades of red. This form of color blindness is not sex-linked.

Anomalous trichromacy

Those with protanomaly, deuteranomaly, or tritanomaly are trichromats, but the color matches they make differ from the normal. They are called anomalous trichromats. In order to match a given spectral yellow light, protanomalous observers need more red light in a red/green mixture than a normal observer, and deuteranomalous observers need more green. From a practical standpoint though, many protanomalous and deuteranomalous people have very little difficulty carrying out tasks that require normal color vision. Some may not even be aware that their color perception is in any way different from normal.

Protanomaly and deuteranomaly can be diagnosed using an instrument called an anomaloscope, which mixes spectral red and green lights in variable proportions, for comparison with a fixed spectral yellow. If this is done in front of a large audience of males, as the proportion of red is increased from a low value, first a small proportion of the audience will declare a match, while most will see the mixed light as greenish; these are the deuteranomalous observers. Next, as more red is added the majority will say that a match has been achieved. Finally, as yet more red is added, the remaining, protanomalous, observers will declare a match at a point where normal observers will see the mixed light as definitely reddish.

Protanomaly (1% of males, 0.01% of females):[22] Having a mutated form of the long-wavelength (red) pigment, whose peak sensitivity is at a shorter wavelength than in the normal retina, protanomalous individuals are less sensitive to red light than normal. This means that they are less able to discriminate colors, and they do not see mixed lights as having the same colors as normal observers. They also suffer from a darkening of the red end of the spectrum. This causes reds to reduce in intensity to the point where they can be mistaken for black. Protanomaly is a fairly rare form of color blindness, making up about 1% of the male population. Both protanomaly and deuteranomaly are carried on the X chromosome.

Deuteranomaly (most common — 6% of males, 0.4% of females):[22] These individuals have a mutated form of the medium-wavelength (green) pigment. The medium-wavelength pigment is shifted towards the red end of the spectrum resulting in a reduction in sensitivity to the green area of the spectrum. Unlike protanomaly the intensity of colors is unchanged. This is the most common form of color blindness, making up about 6% of the male population. The deuteranomalous person is considered "green weak". For example, in the evening, dark green cars appear to be black to Deuteranomalous people. Similar to the protanomates, deuteranomates are poor at discriminating small differences in hues in the red, orange, yellow, green region of the spectrum. They make errors in the naming of hues in this region because the hues appear somewhat shifted towards red. One very important difference between deuteranomalous individuals and protanomalous individuals is deuteranomalous individuals do not have the loss of "brightness" problem.

Tritanomaly (equally rare for males and females [0.01% for both]):[22] Having a mutated form of the short-wavelength (blue) pigment. The short-wavelength pigment is shifted towards the green area of the spectrum. This is the rarest form of anomalous trichromacy color blindness. Unlike the other anomalous trichromacy color deficiencies, the mutation for this color blindness is carried on chromosome 7. Therefore it is equally prevalent in both male &female populations. The OMIM gene code for this mutation is 304000 "Colorblindness, Partial Tritanomaly".[23]

Total color blindness

Achromatopsia is strictly defined as the inability to see color. Although the term may refer to acquired disorders such as cerebral achromatopsia also known as color agnosia, it typically refers to congenital color vision disorders (i.e. more frequently rod monochromacy and less frequently cone monochromacy).[24]

In cerebral achromatopsia, a person cannot perceive colors even though the eyes are capable of distinguishing them. Some sources do not consider these to be true color blindness, because the failure is of perception, not of vision. They are forms of visual agnosia.[24]

Red–green color blindness

X-linked recessive inheritance

Protanopia, deuteranopia, protanomaly, and deuteranomaly are widely common inherited colour blindness that affects a substantial portion of the human population, in which those affected have difficulty with discriminating red and green hues due to the absence of the red or green retinal photoreceptors, respectively.[25] [26] It is sex-linked: genetic red–green color blindness affects males much more often than females, because the genes for the red and green color receptors are located on the X chromosome, of which males have only one and females have two. Females (46, XX) are red–green color blind only if both their X chromosomes are defective with a similar deficiency, whereas males (46, XY) are color blind if their single X chromosome is defective.

The gene for red–green color blindness is transmitted from a color blind male to all his daughters who are heterozygote carriers and are usually unaffected. In turn, a carrier woman has a fifty percent chance of passing on a mutated X chromosome region to each of her male offspring. The sons of an affected male will not inherit the trait from him, since they receive his Y chromosome and not his (defective) X chromosome. Should an affected male have children with a carrier or colorblind woman, their daughters may be colorblind by inheriting an affected X chromosome from each parent.

Because one X chromosome is inactivated at random in each cell during a woman's development, it is possible for her to have four different cone types, as when a carrier of protanomaly has a child with a deuteranomalic man. Denoting the normal vision alleles by P and D and the anomalous by p and d, the carrier is PD pD and the man is Pd. The daughter is either PD Pd or pD Pd. Suppose she is pD Pd. Each cell in her body expresses either her mother's chromosome pD or her father's Pd. Thus her red–green sensing will involve both the normal and the anomalous pigments for both colors. Such females are tetrachromats, since they require a mixture of four spectral lights to match an arbitrary light.

Blue–yellow color blindness

Those with tritanopia and tritanomaly have difficulty discriminating blueish versus yellowish hues.

Color blindness involving the inactivation of the short-wavelength sensitive cone system (whose absorption spectrum peaks in the bluish-violet) is called tritanopia or, loosely, blue–yellow color blindness. The tritanopes neutral point occurs near a yellowish 570 nm; green is perceived at shorter wavelengths and red at longer wavelengths. Mutation of the short-wavelength sensitive cones is called tritanomaly. Tritanopia is equally distributed among males and females. Jeremy H. Nathans (with the Howard Hughes Medical Institute) proved that the gene coding for the blue receptor lies on chromosome 7, which is shared equally by males and females. Therefore it is not sex-linked. This gene does not have any neighbor whose DNA sequence is similar. Blue color blindness is caused by a simple mutation in this gene.

Diagnosis

Example of an Ishihara color test plate.[Note 1] The numeral "74" should be clearly visible to viewers with normal color vision. Viewers with dichromacy or anomalous trichromacy may read it as "21", and viewers with achromatopsia may not see numbers.

An Ishihara test image as seen by subjects with normal color vision and by those with a variety of color deficiencies

The Ishihara color test, which consists of a series of pictures of colored spots, is the test most often used to diagnose red–green color deficiencies. A figure (usually one or more Arabic digits) is embedded in the picture as a number of spots in a slightly different color, and can be seen with normal color vision, but not with a particular color defect. The full set of tests has a variety of figure/background color combinations, and enable diagnosis of which particular visual defect is present. The anomaloscope, described above, is also used in diagnosing anomalous trichromacy.

Because the Ishihara color test contains only numerals, it may not be useful in diagnosing young children, who have not yet learned to use numerals. In the interest of identifying these problems early on in life, alternative color vision tests were developed using only symbols (square, circle, car).

Besides the Ishihara color test, the US Navy and US Army also allow testing with the Farnsworth Lantern Test. This test allows 30% of color deficient individuals, whose deficiency is not too severe, to pass.

Most clinical tests are designed to be fast, simple, and effective at identifying broad categories of color blindness. In academic studies of color blindness, on the other hand, there is more interest in developing flexible tests to collect thorough datasets, identify copunctal points, and measure just noticeable differences.[27]

Management

Neil Harbisson uses an eyeborg to overcome his Achromatopsia

There is generally no treatment to cure color deficiencies. Optometrists can supply colored spectacle lenses or a single red-tint contact lens to wear on the non-dominant eye but, although this may improve discrimination of some colors it can make other colors more difficult to distinguish. A 1981 review of various studies to evaluate the effect of the X-chrom contact lens concluded that, while the lens may allow the wearer to achieve a better score on certain color vision tests, it did not correct color vision in the natural environment.[28]

The GNOME desktop environment provides colorblind accessibility using the gnome-mag and the libcolorblind software. Using a gnome applet, the user may switch a color filter on and off choosing from a set of possible color transformations that will displace the colors in order to disambiguate them. The software enables, for instance, a color blind person to see the numbers in the Ishihara test.

A lot of applications for iPhone and iPad have been developed to help colorblind people to view the colors in a better way. Many apps launch a sort of simulation of colorblind vision to make normal view people understand how the colorblinds see the world. Others ones allow a correction of the image grabbed from the camera with a special "daltonizer" algorithm.

In September 2009, the journal Nature reported that researchers at the University of Washington and University of Florida were able to give trichromatic vision to squirrel monkeys, which normally have only dichromatic vision, using gene therapy.[29]

In 2003, a cybernetic device called eyeborg was developed to allow the wearer to hear sounds representing different colors.[30] Achromatopsic artist Neil Harbisson was the first to use such a device in early 2004, the eyeborg allowed him start painting in color by memorizing the sound corresponding to each colour. In 2012 at a TED Conference, Harbisson explained how he could now perceive colors outside the ability of human vision.[31]

Epidemiology

Color blindness affects a significant number of people, although exact proportions vary among groups. In Australia, for example, it occurs in about 8 percent of males and only about 0.4 percent of females. Isolated communities with a restricted gene pool sometimes produce high proportions of color blindness, including the less usual types. Examples include rural Finland, Hungary, and some of the Scottish islands. In the United States, about 7 percent of the male population – or about 10.5 million men – and 0.4 percent of the female population either cannot distinguish red from green, or see red and green differently from how others do (Howard Hughes Medical Institute, 2006). More than 95 percent of all variations in human color vision involve the red and green receptors in male eyes. It is very rare for males or females to be "blind" to the blue end of the spectrum.

	Males	Females	Total	References
Red–green (Overall)	7 to 10%	0.49 to 1%	—
Red–green (Caucasians)	8%	0.0064%	—
Red–green (Asians)	5%	0.0025	—
Red–green (Africans)	4%	0.0016%	—
Monochromacy	—	—	—
Rod monochromacy (dysfunctional, abnormally shaped or no cones)	0.00001%	0.00001%	—
Dichromacy	2.4%	0.03%	1.30%
Protanopia (red deficient: L cone absent)	1% to 1.3%	0.02%	—
Deuteranopia (green deficient: M cone absent)	1% to 1.2%	0.01%	—
Tritanopia (blue deficient: S cone absent)	0.03%	0.001%	—
Anomalous Trichromacy	6.3%	0.37%	—
Protanomaly (red deficient: L cone defect)	1.3%	0.02%	—
Deuteranomaly (green deficient: M cone defect)	5.0%	0.35%	—
Tritanomaly (blue deficient: S cone defect)	0.01%	0.01%	—

Society and culture

Design implications of color blindness

Testing the colors of a web chart, (center), to ensure that no information is lost to the various forms of color-blindness.

Color codes present particular problems for those with color deficiencies as they are often difficult or impossible for them to perceive.

Good graphic design avoids using color coding or using color contrasts alone to express information; this not only helps color blind people, but also aids understanding by normally sighted people.

Designers need to take into account that color-blindness is highly sensitive to differences in material. For example, a red–green colorblind person who is incapable of distinguishing colors on a map printed on paper may have no such difficulty when viewing the map on a computer screen or television. In addition, some color blind people find it easier to distinguish problem colors on artificial materials, such as plastic or in acrylic paints, than on natural materials, such as paper or wood. Third, for some color blind people, color can only be distinguished if there is a sufficient "mass" of color: thin lines might appear black while a thicker line of the same color can be perceived as having color.[citation needed]

Designers should also note that red-blue and yellow-blue color combinations are generally safe. So instead of the ever popular "red means bad and green means good" system, using these combinations can lead to a much higher ability to use color coding effectively. This will still cause problems for those with monochromatic color blindness, but it is still something worth considering.

When the need to process visual information as rapidly as possible arises, for example in an emergency situation, the visual system may operate only in shades of gray, with the extra information load in adding color being dropped.[citation needed] This is an important possibility to consider when designing, for example, emergency brake handles or emergency phones.

Occupations

Color blindness may make it difficult or impossible for a person to engage in certain occupations. Persons with color blindness may be legally or practically barred from occupations in which color perception is an essential part of the job (e.g., mixing paint colors), or in which color perception is important for safety (e.g., operating vehicles in response to color-coded signals). This occupational safety principle originates from the Lagerlunda train crash of 1875 in Sweden. Following the crash, Professor Alarik Frithiof Holmgren, a physiologist, investigated and concluded that the color blindness of the engineer (who had died) had caused the crash. Professor Holmgren then created the first test using different-colored skeins to exclude people from jobs in the transportation industry on the basis of color blindness.[32] However there is a claim that there is no ﬁrm evidence that color deﬁciency did cause the collision, and that it might have not been the sole cause.[33]

Color vision is important for occupations using telephone or computer networking cabling, as the individual wires inside the cables are color-coded using green, orange, brown, blue and white colors.[34] Electronic wiring, transformers, resistors, and capacitors are color-coded as well, using black, brown, red, orange, green,

yellow, blue, violet, gray, white, silver, gold.[35]

Driving motor vehicles

Some countries (for example, Romania) have refused to grant driving licenses to individuals with color blindness. In Romania, there is an ongoing campaign to remove the legal restrictions that prohibit colorblind citizens from getting drivers' licenses.[36]

The usual justification for such restrictions is that drivers of motor vehicles must be able to recognize color-coded signals, such as traffic lights or warning lights.

Piloting aircraft

While many aspects of aviation depend on color coding, only a few of them are critical enough to be interfered with by some milder types of color blindness. Some examples include color-gun signaling of aircraft that have lost radio communication, color-coded glide-path indications on runways, and the like. Some jurisdictions restrict the issuance of pilot credentials to persons who suffer from color blindness for this reason. Restrictions may be partial, allowing color-blind persons to obtain certification but with restrictions, or total, in which case color-blind persons are not permitted to obtain piloting credentials at all.

In the United States, the Federal Aviation Administration requires that pilots be tested for normal color vision as part of their medical clearance in order to obtain the required medical certificate, a prerequisite to obtaining a pilot's certification. If testing reveals color blindness, the applicant may be issued a license with restrictions, such as no night flying and no flying by color signals—such a restriction effectively prevents a pilot from holding certain flying occupations, such as that of an airline pilot, although commercial pilot certification is still possible, and there are a few flying occupations that do not require night flight and thus are still available to those with restrictions due to color blindness (e.g., agricultural aviation). The government allows several types of tests, including medical standard tests (e.g., the Ishihara, Dvorine, and others) and specialized tests oriented specifically to the needs of aviation. If an applicant fails the standard tests, he or she will receive a restriction on their medical certificate that states- "Not valid for night flying or by color signal control." He/she may apply to the FAA to take a specialized test, administered by the FAA. Typically, this test is the "color vision light gun test." For this test an FAA inspector will meet the pilot at an airport with an operating control tower, and the color signal light gun will be shone at the pilot from the tower, and he or she must identify the color. If he passes, he may be issued a waiver, which states that the color vision test is no longer required during medical examinations. He will then receive a new medical certificate with the restriction removed. This was once a Statement of Demonstrated Ability (SODA), but the SODA was dropped, and converted to a simple waiver (letter) early in the 2000s.[37]

Research published in 2009 carried out by the City University of London's Applied Vision Research Centre, sponsored by the UK's Civil Aviation Authority and the US Federal Aviation Administration, has established a more accurate assessment of color deficiencies in pilot applicants' red–green and yellow–blue color range which could lead to a 35% reduction in the number of prospective pilots who fail to meet the minimum medical threshold.[38]

Art

Inability to distinguish color does not necessarily preclude the ability to become a celebrated artist. The expressionist painter Clifton Pugh, three-time winner of Australia's Archibald Prize, on biographical, gene inheritance and other grounds has been identified as a protanope.[39] 19th century French artist Charles Méryon became successful by concentrating on etching rather than painting after he was diagnosed as having a red–green deficiency.[40]

Rights of people with color blindness

Brazil

A Brazilian court ruled that people with color blindness are protected by the Inter-American Convention on the Elimination of All Forms of Discrimination against Person with Disabilities.[41][42][43]

At trial, it was decided that the carriers of color blindness have a right of access to wider knowledge, or the full enjoyment of their human condition.

Problems and compensations

Simulation of the normal (above) and dichromatic (below) perception of red and green apples.

Horizontal traffic light in Halifax, NS Canada

Color blindness very rarely means complete monochromatism. In almost all cases, color blind people retain blue–yellow discrimination, and most color-blind individuals are anomalous trichromats rather than complete dichromats. In practice this means that they often retain a limited discrimination along the red–green axis of color space, although their ability to separate colors in this dimension is severely reduced.

Dichromats often confuse red and green items. For example, they may find it difficult to distinguish a Braeburn apple from a Granny Smith and in some cases, the red and green of traffic light without other clues (for example, shape or position). The vision of dichromats may also be compared to images produced by a color printer that has run out of the ink in one of its three color cartridges (for protanopes and deuteranopes, the magenta cartridge, and for tritanopes, the yellow cartridge). Dichromats tend to learn to use texture and shape clues and so are often able to penetrate camouflage that has been designed to deceive individuals with color-normal vision.[4]

Traffic light colors are confusing to some dichromats as there is insufficient apparent difference between the red/amber traffic lights, and that of sodium street lamps; also the green can be confused with a grubby white lamp. This is a risk factor on high-speed undulating roads where angular cues cannot be used. British Rail color lamp signals use more easily identifiable colors: the red is blood red, the amber is yellow and the green is a bluish color. Most British road traffic lights are mounted vertically on a black rectangle with a white border (forming a "sighting board") and so dichromats can look for the position of the light within the rectangle — top, middle or bottom. In the Eastern provinces of Canada horizontally mounted traffic lights are generally differentiated by shape to facilitate identification for those with color blindness.

See also

Cerebral achromatopsia

Ishihara color test

Farnsworth Lantern Test

Motion blindness

Tetrachromacy

References

Explanatory notes

^ a b c d Because of variations in computer displays, these illustrations may not be accurately rendered.

Citations

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^ "Inter-American Convention on the Elimination of All Forms of Discrimination against Person with Disabilities.". http://www.oas.org/juridico/english/ga-res99/eres1608.htm. Retrieved 2012-03-09.Prevalence of color blindness

출처: http://en.wikipedia.org/wiki/Color_blindness

* X-연관 열성유전 남자의 경우 자식을 낳는 경우도 있다: 딸은 모두 보인자, 아들은 정상

(Fig.8.6)

8.4 X-연관 우성유전

* Vitamin D 내성 구루병: 남, 여 모두 같이 발병, 여자의 경우 lyonization 에 의해 증상이 다를 수 있음.(Fig.8.8)

* 가계도: 상염색체성 우성유전과 비슷하나, male-to-male 유전이 없다(Table 8.1)

* Xg 혈액형, incontinentia pigmenti(NEMO (NF-kappaB essential modulator: NF-kappaB 활성에 관여) 유전자 결핍, 여성에게만 오는 유전질환, 색소실조증, 수포-->사마귀모양 색소침착, 뼈 및 중추신경 기형 동반),  Rett 증후군(MeCP2 gene: methyl-CpG binding protein)(Table 8.3)

Hemizygous: Having only a single copy of a gene instead of the customary two copies. All of the gene on the single X chromosome in the male are in the hemizygous state

Xga Blood Group System

Inheritance

The Xga (or Xg) system is one of the few BGS whose genes are sex-linked. Because the system has little significance other than its mode of inheritance, it is included in this chapter. As the name implies, the gene locus is on the X chromosome. Inheritance is controlled by two alleles (Xga and Xg) with Xga being dominant and Xg being recessive (or an amorph).

Because the system is sex-linked, the frequency of the Xg(a+) phenotype varies in males and females. The female frequency is 88% and the male frequency is 66%.

Males can be positive (XgaY) or negative (XgY). If positive, they are said to be hemizygous.

Females, if positive, can be homozygous (XgaXga) or heterozygous (XgaXg). XgXg females are Xg(a-).