Genética hereditária: pesquisas atuais

Abstrato

Identification of Two Novel Mutations in the SLC45A2 Gene in a Hungarian Pedigree Affected by Unusual OCA Type 4

Tóth L, Fábos B, Farkas K, Sulák A, Tripolszki K, Széll M and Nagy N

Oculocutaneous Albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities. OCA type IV (OCA4, OMIM 606574) develops due to homozygous or compound heterozygous mutations in the solute carrier family 45, member 2 (SLC45A2) gene. This gene encodes a membrane-associated transport protein, which regulates tyrosinase activity and, thus, melanin content by changing melanosomal pH and disrupting the incorporation of copper into tyrosinase. Here we report two Hungarian siblings affected by an unusual OCA4 phenotype. Direct sequencing of the SLC45A2 gene revealed two novel, heterozygous mutations, one missense (c.1226G/A p.Gly411Asp) and one nonsense (c.1459C/T p.Gln437X), which were present in both patients, suggesting the mutations were compound heterozygous. The identified novel mutations affect the transmembrane domains of the protein, indicating that they might impair transport function, resulting in decreases in both melanosomal pH and tyrosinase activity. Our study provides new insights to the genetic background of OCA4 by reporting an unusual OCA4 phenotype and expanding the mutation spectrum of the SLC45A2 gene.