Oral communication, CS23 / C112

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

Albinochip: a universal genetic diagnosis for all known mutations associated to albinism

Albinism is a rare disease affecting 1:17000 Europeans. There are several types of albinism, globally characterised by hypopigmentation, affecting skin, hair and eyes (in oculocutaneous albinism, OCA) or mainly eyes (in ocular albinism, OA), and by a profound visual impairment, for which they are primarily handicapped. Severe and rarer forms of albinism show additional symptoms, including increased infections, bleeding problems and bruising (Hermansky-Pudlak syndrome, HPS, and Chediak-Higashi syndrome, CHS). At least 14 genes have been identified whose mutations are associated with albinism, namely: TYR (OCA1), OCA2 (OCA2), TYRP1 (OCA3), SLC45A2/MATP (OCA4), GPR143 (OA1), LYST (CHS1), HPS1 (HPS1), AP3B1 (HPS2), HPS3 (HPS3), HPS4 (HPS4), HPS5 (HPS5), HPS6 (HPS6), DTNBP1 (HPS7) and BLOC1S3 (HPS8). All these genes encode proteins that are involved in melanin synthesis, melanosome function or lysosome-related organelle biogenesis. In persons with albinism, besides the characteristic hypopigmented phenotype, the main handicapping feature is their common severe visual deficiencies, leading to legal blindness in most cases. More than 500 mutations have been reported in those 14 loci, causing albinism, as obtained from the literature and human gene mutation databases. Currently, very few institutions in the world offer the genetic diagnosis of albinism for some of the known 14 loci involved. As a result, the vast majority of persons with albinism remain not diagnosed and hence, early detection of this rare genetic condition is prevented, and the establishment of the recommended care and helping measures is unfortunately delayed or missed, thus affecting the life-quality of the patients. In this regard, from the Biomedical Network Research Centre on Rare Diseases (CIBERER) in Spain, in collaboration with experts in albinism from around the world, we have developed a new technological strategy aiming to a universal genetic diagnosis of all types of albinism. This approach uses iPlex methodology, by Sequenom, which combines automated array processing of human subject’s DNA samples with mass spectrometry (MALDI-TOF) and can be applied to discriminate, simultaneously, up to 1000 different alleles with known mutations, from a given DNA sample. Therefore the “albinochip” proposal aims to define a universal genetic test for all known forms of albinism using massive genomic approaches with the aim of detecting any known mutation in any of the affected genes. Moreover, additional new complementary genomic approaches will be designed to reveal new mutations in these and other loci. About 20% of the patients with albinism remain undiagnosed or not fully diagnosed, because either no mutation or only one mutation is found. The mutation search must therefore be improved using novel genomic approaches, including exome sequencing for detecting new mutations and/or new albinism genes. Members of ALBA (www.albinismo.es), the Spanish association in support of persons with albinism, have contributed extensively to this project. Updated results of this collaborative project will be reported. Grant Support: CIBERER INTRA/07/704.1

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