遗传性泛发性色素异常症遗传学研究进展

Genetic advances in dyschromatosis universalis hereditaria

遗传性泛发性色素异常症以常染色体显性遗传模式为主,也可表现为常染色体隐性遗传.近年来该病的分子遗传学研究取得较大进展,找到3个不同致病区域,分别为6q24.2-q25.2、12q21-q23和2q35.发现2q35上的ATP结合盒亚家族B成员6为该病的致病基因,进一步通过基因功能证实,免疫组化显示,ABCB6抗体在上皮细胞质中弥散性分布,蛋白免疫印迹显示,ABCB6在黑素细胞和角质形成细胞中有表达,斑马鱼实验证明了ATP结合盒亚家族B成员6在色素代谢方面起重要作用.目前报道,遗传性泛发性色素异常症的ABCB6基因突变位点共8个,包括1个移码突变,7个错义突变.

Dyschromatosis universalis hereditaria （DUH） is inherited mainly in an autosomal dominant manner,sometimes in an autosomal recessive manner.In recent years,great progress has been made in molecular genetics of DUH.Three pathogenic genetic loci have been reported to be associated with DUH,including 6q24.2-q25.2,12q21-q23 and 2q35.The ATP-binding cassette,sub-family B,member 6 （ABCB6） gene at 2q35 has been identified as a pathogenic gene for DUH by gene function analysis.Immunohistochemical studies showed that anti-ABCB6 antibodies were diffusely distributed in the cytoplasm of epithelial cells,Western blot analysis revealed that ABCB6 was expressed in melanocytes and keratinocytes,and zebrafish assays demonstrated that ABCB6 played an important role in pigment metabolism.By now,8 mutations of the ABCB6 gene have been reported in patients with DUH,including 1 frameshift mutation and 7 missense mutations.