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Human genetics

Molecular analysis of type I-A (tyrosinase negative) oculocutaneous albinism.


PMID 1487241

Abstract

Type I oculocutaneous albinism (OCA) is caused by the reduction in or absence of activity of tyrosinase in melanocytes in skin, hair, and the eyes, the result of mutations of the tyrosinase gene. To date, a total of 22 unique mutations in the coding region of tyrosinase have been described in the literature. In this report we present 5 additional mutations of the tyrosinase gene associated with type I-A OCA in four individuals, including 2 missense, 1 frameshift and 2 nonsense mutations, and review the relevant literature on all published mutations. Analysis of the distribution of all identified missense mutations (n = 17) shows that most cluster in three areas of the gene and involve amino acids conserved between humans and the mouse. Two clusters involve the copper A and copper B binding sites and may disrupt the metal ion-protein interaction necessary for enzyme function. The third cluster in exon I could represent a functional domain important in enzyme function such as the tyrosine or the dihydroxyphenylalanine (DOPA) binding site of the enzyme. Small deletions or insertions resulting in frameshift mutations and nonsense mutations are distributed throughout the coding region and do not appear to cluster.