背景:雄激素不敏感综合征是一种由雄激素受体基因(AR)突变引起的X连锁隐性遗传病。然而,大多数AR变异的潜在分子机制尚不清楚.在这项研究中,我们在3例完全雄激素不敏感综合征(CAIS)患者中发现了一个点变异,总结了相关分析,并进行了文献综述。
方法:先证者是女孩长大的。在婴儿期,她第一次因为右腹股沟疝被转诊到医院。超声检查显示没有子宫和卵巢,和位于腹股沟管的睾丸样结构。进一步的诊断检查检测到46,XY核型,荧光原位杂交分析表明存在SRY基因。组织学分析显示切除的组织是睾丸。十二年后,她因乳房发育不足而入院。她的阴毛和乳房是Tanner阶段。她有正常的女性外生殖器。血液激素检测显示睾酮水平正常,低雌二醇水平,和高促性腺激素水平。她的两个兄弟姐妹接受了类似的检查,这三个人在AR中都有一个罕见的半合子错义突变:c.2678C>T。体外功能分析显示AR-c.2678C>T突变细胞的核易位减少。
结论:该病例是由AR变异引起的(c.2678C>T)。功能研究表明,突变蛋白的核易位能力受损。
BACKGROUND: Androgen insensitivity syndrome is an X-linked recessive genetic disease caused by mutations in the androgen receptor gene (AR). However, the underlying molecular mechanisms for the majority of AR variants remain unclear. In this study, we identified a point variant in three patients with complete androgen insensitivity syndrome (CAIS), summarized the correlation analysis, and performed a literature review.
METHODS: The proband was raised as a girl. In infancy, she was first referred to hospital with a right inguinal hernia. Ultrasonography revealed the absence of a uterus and ovaries, and a testis-like structure located at the inguinal canal. Further diagnostic workup detected a 46, XY karyotype, and fluorescence in situ hybridization analysis showed the presence of the SRY gene. Histological analysis revealed the excised tissue to be testicular. Twelve years later, she was admitted to our hospital with a lack of breast development. Her pubic hair and breasts were Tanner stage I. She had normal female external genitalia. Blood hormone tests showed normal testosterone levels, low estradiol levels, and high gonadotropin levels. Her two siblings underwent similar examinations, and all three had a rare hemizygous missense mutation in AR: c.2678C>T. In vitro functional analyses revealed decreased nuclear translocation in AR-c.2678C>T mutation cells.
CONCLUSIONS: This
case of CAIS was caused by an AR variant (c.2678C>T). Functional studies showed impaired nuclear translocation ability of the mutant protein.