完全雄激素不敏感综合征
雄激素不敏感综合征
雄激素受体
桑格测序
突变
生物
雄激素
遗传学
遗传咨询
性发育障碍
基因
男性不育
表型
内分泌学
内科学
医学
不育
激素
癌症
前列腺癌
怀孕
作者
Xuanyu Jiang,Yuanwen Teng,Xin Chen,Nana Liang,Zhuo Li,Desheng Liang,Lingqian Wu
标识
DOI:10.1016/j.cca.2020.03.036
摘要
Androgen insensitivity syndrome (AIS) is the most common type of 46, XY disorders of sex development (DSD), with a wide range of clinical heterogeneity, from male infertility, hypospadias to completely normal female external genitalia. Mutation of the androgen receptor (AR) gene on the X chromosome (Xq11.2q12) is the main cause of AIS. By phenotype evaluation, hormone test, ultrasound scan and G-banding karyotype, 17 unrelated Chinese patients were clinical diagnosed with AIS. Sanger sequencing of the AR was performed in these 17 patients. Functional studies were carried out for the novel mutations. We identified 16 mutations in all patients, including six novel mutations (Q59*, F171Sfs*4, E204*, G209E, I870T, *921R). It is the first time that a stop codon mutation (*921R) in AR has been identified. Expression and nuclear localization analysis showed the *921R mutation caused an elongated abnormal polypeptide chain of the AR protein, and the abnormal protein could not be transported to the nucleus to stimulate the expression of downstream genes after androgenic treatment. Expression analysis showed the protein level of G209E mutation was obviously decreased. Our study expands the spectrum of AR mutations and could provide evidence for the genetic and reproductive counseling of families with AIS. All of these findings broadened the mutation spectrum of AR, which were significantly valuable for patient gender assignment, genetic counseling and the clinical and psychological management.
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