Molecular basis of type IA (tyrosinase negative) oculocutaneous albinism

Type IA (Tyrosinase negative) oculocutaneous albinism (OCA) is produced by mutations of the tyrosinase gene. We have found a total of 13 different mutations associated with type IA OCA. Analysis of the distribution of the 9 missense mutations shows that most of these mutations cluster in three areas of the gene. All but one of these mutations involve amino acids that are conserved between the mouse and human. Two clusters involve the copper A and copper B binding sites, and could disrupt the metal ion-protein interaction necessary for enzyme function. The third cluster is in exon I and could represent an important functional domain of the enzyme such as the tyrosine binding site. The deletion or insertion frameshift mutations are distributed throughout the coding region and do not appear to cluster. We conclude that a diverse number of mutations are responsible for type IA OCA and many individuals are compound heterozygotes for mutations responsible for this genetic disease (Table 3).