雄激素受体基因新突变引起的完全型雄激素不敏感综合征

A novel mutation Glu441stop （GAA to TAA） of androgen receptor gene resulting in complete androgen insensitivity syndrome

目的 对1例完全型雄激素不敏感综合征（complete androgen insensitivity syndrom,CAIS）的雄激素受体（androgen receptor,AR）基因进行分析,寻找致病突变.方法 提取外周血全基因组DNA,扩增位于X染色体上的AR基因所有8个外显子及邻近外显子与内含子之间的剪切位点DNA序列,对扩增片段直接进行DNA序列测定,与基因库中的序列进行比对.结果 该病例AR基因第1外显子的441位密码子发生无义突变（GAA→TAA）,由编码谷氨酸（Glu）变为终止密码,导致雄激素受体蛋白翻译至441位时终止,产生没有功能的氨基酸多肽残段.结论 Glu441stop（GAA→TAA）是一种导致CAIS的AR基因新的突变方式,之前在世界范围内均未见报道,丰富了AR基因突变谱,增加对CAIS发病机制的了解.

Objective To identify the mutation of human androgen receptor gene（AR） in a patient with complete androgen insensitivity syndrome （CAIS）. Methods DNA sequences of 8 exons and their exon/intron boundaries of the AR gene in the patient were amplified by PCR and directly sequenced. Results DNA sequencing revealed a nonsense mutation in exon 1, resulting in a change of codon 441 GAA （glutamic acid） to a stop codon （TAA）. Conclusion A novel mutation Glu441stop （GAA to TAA） of the androgen receptor gene leading to complete androgen insensitivity syndrome was identified in this study in a Chinese patient. It may help us further understanding the pathogenesis of CAIS.