Oculocutaneous albinism type 1, 2, 3 and 4 (Oculocutaneous albinism types 1, 2, 3 and 4) - Genes TYR, OCA2, TYRP1, SLC45A2 and MC1R

Oculocutaneous albinism (OCA: Cutaneous Albinism oculo-) is a group of diseases that affect pigmentation of the skin, hair and eyes. People usually have very white skin and hair white or light colored. sun exposure for a long time considerably increases the risk of skin damage and skin cancer, including melanoma. Oculocutaneous albinism also reduces the pigmentation of the iris and the retina. As a result, affected individuals usually manifest vision problems, such as decrease in visual acuity, nystagmus and photophobia.

Described so far Oculocutaneous 4 types of albinism, which are distinguished by specific changes in skin color, hair and eyes, as well as its genetic cause. The oculocutaneous albinism type 1 (OCA1) is characterized by white hair, pale skin, and iris light colored. Type 2 (OCA2) is usually less severe than Type 1, generally being skin creamy white and the hair can be light yellow or light brown blond. The OCA3 phenotype is characterized by skin and reddish hair, which usually affects people with dark skin. Type 3 is often associated with abnormalities in milder than other forms of oculocutaneous albinism vision. Meanwhile, the phenotype 4 (OCA4) is characterized by similar signs and symptoms observed in OCA2. It should be noted that the oculo-cutaneous albinism is a component of at least 3 other syndromes: (genes HPS1 and HPS4, among others), Chediak-Higashi syndrome (CHS: Hermansky-Pudlak (Hermansky-Pudlak Syndrome HPS) syndrome : Chediak-Higashi syndrome) (LYST gene - CHS1 -) and Griscelli (GS syndrome: Griscelli syndrome) (MYO5A genes, RAB27A, MLPH).

The oculocutaneous albinism may be due to mutations in several genes, including TYR (OCA1), OCA2 (OCA2), TYRP1 (OCA3), and SLC45A2 (OCA4). Some individuals with oculocutaneous albinism have mutations in any of the known genes. In these people, the genetic cause of the disease is unknown. Genes associated with oculocutaneous albinism encode proteins or enzymes found in melanocytes and are involved in melanin production. In the retina, melanin also plays a role in normal vision. Mutations in any of these genes alter the ability of cells to produce melanin, reducing pigmentation in skin, hair and eyes. Lack of melanin in the retina leads to vision problems characteristic of Oculocutaneous albinism.

The TYR gene, located on the long arm of chromosome 11 (11q14.3), encodes the enzyme tyrosinase, responsible for the first step in the production of melanin. Specifically converts the amino acid tyrosine to another compound called dopaquinone. A number of additional chemical reactions transformed dopaquinone melanin in skin, hair follicles, iris and retina. They described over 100 mutations in the gene TYR in people with oculocutaneous albinism type 1 (OCA1). These mutations alter the normal production of melanin, reducing hair coloring, skin and eyes and cause vision problems. Most of these mutations eliminated the activity of tyrosinase, preventing melanin production by melanocytes. These mutations cause a form of oculocutaneous albinism called type 1A (OCA1A). People with this form of albinism have white hair, light colored eyes, and very pale skin that does not tan. Other mutations in the gene TYR reduced but not eliminated tyrosinase activity. These mutations, which allow some melanin production, type 1B cause oculocutaneous albinism type (OCA1B). People with type 1B also born with white hair, blue eyes and pale skin, but hair and eye color often darkens over time and the skin can tan.

The OCA2, formerly called the P gene, located on the long arm of chromosome 15 (15q) encoding the P protein Although the exact function of the P protein is unknown, it is essential for normal pigmentation and is likely involved in the melanin production. In addition, it is believed that this protein may also help regulate the pH of melanosomes. They have identified more than 80 mutations in the OCA2 gene in people with albinism type 2 Oculocutaneous most frequent mutation is a deletion in the gene, which is found in many affected individuals from sub - Saharan African heritage. Other mutations OCA2, including changes in pairs and small deletions, are more common in other populations. Mutations in the gene OCA2 disrupt the normal production of melanin, reducing hair coloring, skin and eyes and affect vision. The oculocutaneous albinism type 2 also occurs in a small number of people with Prader-Willi syndrome.

The TYRP1 gene, located on the short arm of chromosome 9 (9p23) encoding tyrosinase 1. It is believed that this enzyme may help stabilize the tyrosinase encoded from the TYR gene, besides determining the shape of melanosomes. Mutations in the gene TYRP1 give rise to oculocutaneous albinism type 3 (OCA3). TYRP1 two mutations are known to cause this form of albinism in Africa individuals. A mutation, or S166X Ser166Ter affects the amino acid serine at position 166. The other mutation, 368delA eliminates a nucleotide in the gene TYRP1. Other alterations have been described in this gene in some affected individuals not African heritage. Most mutations result TYRP1 encoding an abnormally short, nonfunctional version of tyrosinase - related protein-1. Because this enzyme plays a role in normal pigmentation, loss leads to changes in skin, hair, and eye color that are characteristic of Oculocutaneous albinism.

The SLC45A2 gene, also called MATP, located on the short arm of chromosome 5 (5p13.2), encodes a protein, although its exact function is unknown, is likely to be involved in melanin production. This protein probably carries molecules necessary for the normal function of melanosomes. It is believed that certain polymorphisms in the SLC45A2 gene may be associated with normal differences in skin, hair and eye color. At least 20 mutations in the SLC45A2 gene are responsible oculocutaneous albinism type 4 (OCA4). The most frequent mutation in the Japanese population replaces the aspartic acid amino acid with the amino acid asparagine at position 157 of the protein (Asp157Asn or D157N). Other mutations, including single amino acid changes or insertions and deletions of genetic material in the SLC45A2 gene has also been reported in several populations around the world. Mutations in this gene reduce or eliminate protein function of SLC45A2 in melanin production.

In addition to mutations in TYR, OCA2, TYRP1 and SLC45A2 gene, alterations in another gene called MC1R, located on the long arm of chromosome 16 (16q24.3), can change the appearance of people with oculocutaneous albinism type 2. This gene helps regulate melanin production and is responsible for some normal variation in pigmentation. People with genetic changes in both the OCA2 gene, as in gene MC1R have many common features of Oculocutaneous albinism type 2, including eye color and vision problems. However, they usually have red hair instead of the usual yellow, blond or light brown seen in this phenotype.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection associated mutations conalbinismo Oculocutaneous types 1, 2, 3 and 4, by the complete PCR amplification of the exons of TYR, OCA2, TYRP1, SLC45A2 and MC1R gene, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).