The Genetics of Albinism in People

Albinism refers to hypopigmentation in the hair, skin, or eyes (in the last case, it’s accompanied by a loss of vision). Its forms vary by the location and amount of pigment loss and are usually rare. The most common type of albinism, which involves moderate but not complete pigment loss, occurs in one out of 15,000 people internationally.

The loss of pigmentation is caused by either (a) melanin production or distribution problems or (b) regeneration problems in melanosomes, the organelles that house melanin. There are a number of genetic mutations that can cause melanin-related abnormalities; each mutation presents with distinct phenotypic features.

There are several forms of albinism. The first, Oculocutaneous albinism (OCA) type 1, involves the absence of melanin in the skin, hair, and eyes as well as vision problems. (If you study the word oculocutaneous, this makes sense—both the eyes (oculo) and skin (cutaneous) are affected.) OCA types 2, 3, and 4 are milder forms of OCA type 1: they involve partial, not total, pigment loss in these areas.

Ocular albinism affects melanin production only in the eyes, and presents with visual difficulties.

Chediak-Higashi Syndrome (CHS) involves total or near-total loss of skin, hair, and eye pigmentation, like people with OCA type 1. The difference lies in the quality of a person's hair, which looks metallic; their respiratory problems; and further hypopigmentation in leukocytes, platelets, and reticular cells. This last deficiency manifests as well in another form of albinism, Hermansky-Pudlak Syndrome (HPS).

Griscelli Syndrome (GS), involves mild melanin loss as well as immunological and neurological defects.

Each type of albinism is caused by genetic mutations. OCA types 1, 2, 3 and 4 are all inherited as autosomal recessive traits (they are not located on sex chromosomes and must be present in both gene copies to be inherited). These four types of OCA result from mutations to the TYR, OCA2, TYRP1, and SLC45A2 genes, respectively. Each of these genes, when expressed normally, functions in the production of melanin. Individuals with mutations to these genes can’t synthesize melanin normally and present with the hypopigmentation characteristic of albinism.

Unlike the four types of OCA, OA is a sex-linked trait, caused by a mutation to the X chromosome. (As a result, OA is more common in males, who only have one X chromosome and thus need only one mutant gene, rather than women’s two.) CHS, HPS, and GS are all autosomal recessive, caused by mutation to the LYST, HPS, and RAB27A genes. LYST affects the Golgi body’s functionality (which is crucial to melanosome production), while HPS and RAB27A affect protein synthesis.

All forms of albinism involve a loss of pigmentation. OCA types 1, 2, 3, and 4; CHS; HPS; and GS all are inherited as autosomal recessive traits, while OA is inherited on the X chromosome. Each results from difficulties in synthesizing or distributing melanin.

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Genetics Home Reference: Ocular albinism

Genetics Home Reference: Oculocutaneous albinism