眼皮肤白化病Ⅱ型相关的P基因突变与DNA多态性

眼皮肤白化病Ⅱ型(OCA2)是白化病中最常见的类型,呈常染色体隐性遗传。P基因为其致病基因，定位于15q11.1－q12，由24个外显子和23个内含子构成。P基因编码838个氨基酸残基构成的110 KDa跨膜蛋白，该蛋白含12个跨膜区，其确切功能尚未完全清楚。迄今至少已报道P基因内60种导致OCA2的病理性突变和43种多态性变异。病理突变主要为错义突变、无义突变、移码突变和剪切位点突变，多数位于肽链的C末端，但并不象OCA1的TYR基因突变那样多成簇出现。P基因多态性变异中的大部分位于外显子，这增加了对致病性突变定义的难度，其中一些导致氨基酸替换的多态性变异可能与正常人色素沉着的表型变

Mutations and Polymorphisms of the P Gene

Oculocutaneous albinism typeII(OCA2), the most common type of albinism, is an autosomal recessive disorder. It is caused by mutations in the P gene, which is located on chromosome 15q11.1-q12 and divided into 24 exons and 23 introns. P gene codes for 838-amino-acid integral membrane protein with 12 putative transmembrane domains, but the exact function is not clear yet. There are at least 60 pathologic mutations and 43 non-pathologic polymorphisms have been found. Pathologic mutations include missense mutations, nonsense mutations, frameshift mutations and splice-sit mutations. But unlike TYR gene, most of P gene mutations are located on the C-terminal and don' t cluster in defined regions. It is difficult to define the pathologic mutations since many non-pathologic polymorphisms also lie in exons. Some non-pathologic missense mutations may be associated with phenotypic variation in normally pigmented individuals and need to further study.