一个完全性雄激素不敏感综合征维吾尔族家系雄激素受体基因突变分析

Analysis of androgen receptor gene mutation in complete androgen insensitivity syndrome in a Uygur family

目的分析一个完全性雄激素不敏感综合征维吾尔族家系雄激素受体（AR）基因的突变及其临床特点，探讨该病的发病机制。方法针对该家系内2例临床拟诊为完全性雄激素不敏感综合征的男性假两性畸形患者，利用PCR扩增及DNA测序对AR基因的全部外显子及其剪切位点序列进行突变检测，并在家系及正常人群中验证所发现的突变。结果该家系2例患者临床表现均符合完全性雄激素不敏感综合征。先证者及其妹（社会性别女，染色体性别男）共2例均为AR基因c．2157G〉A，p．W719X的无义突变，其母亲为该突变AR基因的携带者。该突变导致AR基因第4外显子2157位碱基G突变为A，719位TGG密码子突变为TGA（终止密码子）。该无义突变使AR蛋白截短202个氨基酸。正常人群中未发现该无义突变。结论AR基因W719X无义突变是该完全性雄激素不敏感综合征家系的致病突变。

Objective To identify the mutation of androgen receptor （AR） gene in a Uygur family with complete androgen insensitivity syndrome and elucidate its pathogenesis.Methods Two males with pseudohermaphroditism in this family were clinically diagnosed complete androgen insensitivity syndrome and by polymerase chain reaction （PCR） and DNA sequencing,we checked possible mutation of all exons and its splice site in AR gene.Two males with pseudohermaphroditism in this family were clinically diagnosed as complete androgen insensitivity syndrome and confirmed by PCR and DNA sequencing.And the possible mutations of all exons and splice sites in AR gene were examined.Results A proband and another family member had c.2157G 〉 A,p.W719X nonsense mutation of AR gene and their mother was a mutation carrier of AR gene.Substitution （G-〉 A） at position 2 157 of exon 4 of AR resulted in mutation （TGG-〉 TGA） at codon 719 （termination codon）.The nonsense mutation led to a truncation of 202 amino acids in AR protein.The mutations were absent in other family members.Conclusion The nonsense mutation at AR gene W719X,a confirmed cause of disease,is first-ever found in Chinese,especially Uygur population.