雄激素不敏感综合征家系遗传学分析与产前诊断

Genetic analysis and prenatal diagnosis of a family with androgen insensitivity syndrome

目的探讨雄激素不敏感综合征(AIS)患者的雄激素受体(AR)基因突变情况以及相应的遗传咨询和产前诊断。方法应用染色体G显带核型分析技术、基因测序技术检测2013年云南省第一人民医院遗传诊断中心产前诊断的1例AIS患者及家系部分成员的AR基因,然后进行遗传学分析。结果核型分析显示先证者和胎儿的染色体核型为46,XY,先证者检出AR基因第4外显子2069-2071del ACG,母亲为AR基因缺失的携带者。该突变造成AR基因的691位氨基酸(天冬氨酸)的缺失,最后编码了918个氨基酸的截短AR蛋白。正常人群中未发现该突变。结论通过对家系成员的临床遗传学分析确定了1种AR基因病理性新突变,AR基因缺失691位氨基酸(天冬氨酸)的截短突变可引起完全型雄激素不敏感综合征。通过遗传咨询和基因检测,可对该家系做出准确的产前诊断。

Objective To identify mutation types of androgen receptor （AR） in a family with androgen insensitivity syndrome and offer genetic counseling and prenatal diagnosis for this family.Methods G-banded karyotyping and DNA sequencing of AR gene were employed to identify genetic mutation in AIS patients and some other members of the same family, and genetic analysis was carried out. Results All GTG banding result of probands and fetus showed 46, XX.A three nucleotides deletion in exon 4 of the AR gene （2069-2071delACG） was detected in probands, which caused deletion of amino acid Asp691 in AR protein and a truncated protein of 919 aa. Mothers are carrier of this mutation, which was not found in the normal controls.Conclusion The de1691Asp mutation is a novel mutation of the AR protein , which causes complete androgen insensitivity syndrome. The family could be provided with accurate prenatal diaosis by enetic counseling and genetic detcetion.