完全型雄激素不敏感综合征一家系基因诊断并文献复习

摘要：雄激素不敏感综合征（AIS）是由雄激素受体（AR）基因突变引起的罕见的X-连锁隐性遗传病，完全型雄激 素不敏感综合征（CAIS）是AIS中雄激素抵抗程度最严重的一种类型。本文对一个CAIS家系成员AR基因的二代测 序结果进行分析，发现先证者AR基因的第7外显子c.2566C>T发生突变，编码第856位精氨酸的密码子（CGC）改变 为半胱氨酸的密码子（TGC），从而雄激素与AR受体结合受到影响，生物学效应不能有效发挥，临床表现为CAIS。经 Sanger测序验证，先证者妹妹和母亲也发现相同的突变。先证者和其妹妹为半合子突变，母亲为杂合突变。笔者认 为AR基因c.2566C>T（p.Arg856Cys）突变导致姐妹二人患CAIS，该突变遗传自她们的母亲。明确AR基因突变位点， 可为家系再次生育提供指导。

Genetic diagnosis and literature review of a family with complete androgen insensitivity syndrome

Abstract: Androgen insensitivity syndrome (AIS) is a rare X-linked recessive genetic disease caused by the mutation in the androgen receptor (AR). The complete androgen insensitivity syndrome (CAIS) is one of the most severe forms of androgen resistance in AIS. In this paper, the next-generation sequencing of AR gene in a family with CAIS was analyzed. It was found the proband carried one c.2566C>T mutation located on the seventh exon, which led to the replacement of a arginine (Arg) codon (CGC) with a cysteine (Cys) codon (TGC) at amino acid position 856 (p.Arg856Cys). The mutations may interfere with the binding of androgen to the AR, which may lead to impair its activity and then result in CAIS. CAIS was an X-linked recessive disease, Sanger sequencing confirmed that the proband’s mother and sister also showed the same mutation. The proband and her sister carried a homozygous mutations, and her mother carried a heterozygous mutation. The authors believed that the AR gene c.2566C>T (p.Arg856Cys) mutation caused the sisters to suffer from CAIS, which was inherited from their mother. The defined mutation of the AR gene can provide guidance for the family reproduction.