King R A, Oetting W S
Department of Medicine, University of Minnesota, Minneapolis 55455.
Pigment Cell Res. 1992;Suppl 2:249-53. doi: 10.1111/j.1600-0749.1990.tb00380.x.
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).
IA型（酪氨酸酶阴性）眼皮肤白化病（OCA）由酪氨酸酶基因突变引起。我们共发现了13种与IA型OCA相关的不同突变。对9种错义突变的分布分析表明，这些突变大多集中在基因的三个区域。除其中一个突变外，所有这些突变都涉及小鼠和人类之间保守的氨基酸。两个簇涉及铜A和铜B结合位点，可能会破坏酶功能所需的金属离子 - 蛋白质相互作用。第三个簇在外显子I中，可能代表酶的一个重要功能域，如酪氨酸结合位点。缺失或插入移码突变分布在整个编码区域，似乎没有聚集现象。我们得出结论，多种突变导致IA型OCA，许多个体是这种遗传病相关突变的复合杂合子（表3）。
