Oral communication, iL48

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

The genetics of oculocutaneous albinism

Oculocutaneous albinism (OCA) is a rare genetic disease characterized by generalized hypopigmentation of the skin, hair and eye, and by ophthalmologic abnormalities, caused by a deficiency in melanin biosynthesis. The definition of OCA subtypes formerly based upon clinical phenotype has moved towards a molecular classification based upon the identification of the causative genes. OCA is a genetically heterogeneous group of autosomal recessive disorders. There are four types of non-syndromic OCA: OCA1 caused by mutations in the TYR gene in 11q14.3, OCA2 caused by mutations in the OCA2 gene (formerly called P) in 15q11.2-q12, OCA3 caused by mutations in the TYRP1 gene in 9p23 and OCA4 caused by mutations in the SCL45A2 gene (formerly called MATP) in 5p13.3. In addition to OCA, X-linked ocular albinism (OA1) is due to mutations of the GPR143 gene. Syndromic forms of albinism include Piebaldism, Waardenburg syndrome (WS1-4), Hermansky-Pudlak syndrome (HPS1-7), Chediak-Higashi syndrome (CHS), and the very rare Griscelli syndrome (GS1-3). The molecular diagnosis of OCA relies mainly on the analysis of the coding regions of the OCA1-4 genes, searching for point mutations and intragenic microdeletions and microduplications. Although a few population-specific mutations have been found, the relative frequency of the different forms of OCA can be roughly estimated as follows: OCA1 50%, OCA2 30%, OCA3 3%, OCA4 17%. After the analysis of these four major genes, and, in some laboratories, of other genes such as GPR143, those responsible for some of the syndromic forms, and other candidate genes (TYRP2, SLC24A5, SILV, …), about 20% of patients remain without diagnosis, since either only one mutation or no mutation at all is identified. This suggests that other albinism genes remain to be discovered. In addition, it is worth noting that pigmentation is a complex process involving a large number of genes which may act as modifiers of OCA patients’ phenotype.

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