X连锁Alport综合征女性患者临床表型差异的可能机制

The possible mechanisms of variated phenotypes in females of X-linked Alport syndrome

Alport综合征(Alport syndrome,AS)是以血尿、感音神经性耳聋和进行性肾功能减退为临床特点的遗传性肾脏疾病,X连锁显性遗传(X-linked Alport syndrome,XLAS)为其主要遗传方式,因COL4A5和(或)COL4A6基因突变所致。X连锁Alport综合征女性患者临床表型差异很大,轻者无症状或仅表现为镜下血尿,重者有慢性肾功能衰竭,尤其是来自同一家系的女性患者临床表型可以明显不同,这种现象不能完全用COL4A5基因突变类型来解释。近年来,研究显示XLAS女性患者临床表型的差异与COL4A5突变mRNA及基底膜a5(Ⅳ)链的表达量相关,而COL4A5突变mRNA及基底膜a5(Ⅳ)链的表达量不同的机制可能与X染色体失活有关,其他表观遗传学调控方式也可能参与其中。该文就X连锁Alport综合征女性患者临床表型差异的可能机制进行了文献综述。

Alport syndrome（AS）is a hereditary renal disease characterized by hematuria,sensorineural hearing loss,ocular lesions and progressive renal failure.It is mostly inherited in an X-linked pattern,due to mutations in the COL4A5 and/or COL4A6 gene.Females with X-linked Alport syndrome（XLAS）have variated phenotypes,from microscopic hematuria to chronic renal failure.These phenotypes cannot be clarified solely by mutation features of COL4A5 gene.Recent studies showed that the severity of renal disease was related to mutant COL4A5 mRNA expression or epidermal basement membrane alpha 5（Ⅳ）expression in XLAS females,X-inactivation has been suspected to be one of the responsible reasons for this phenomenon,as well as other epigenetic regulation pathways.The literature about the possible mechanisms of the variable phenotypes in XLAS females was reviewed.