Different types of androgen receptor mutations in patients with complete androgen insensitivity syndrome
Different types of androgen receptor mutations in patients with complete androgen insensitivity syndrome
复制标题
完全性雄激素不敏感综合征患者不同类型雄激素受体突变
DOI：
10.5582/irdr.2014.01035
复制
发表时间：
2015-02-01
影响因子：
1.3
通讯作者：
Wang, Xiang
中科院分区：
文献类型：
--
作者：
Shao, Jialiang;Hou, Jiangang;Wang, Xiang
雄激素受体（AR）突变是46，XY性发育障碍的最常见原因，并与各种表型相关，从表型女性（完全雄激素不敏感综合征（CAIS））到轻度男性化不足（部分形式或PAIS）或仅不育的男性（轻度形式或迈斯）。2009年至2012年，来自两个家庭的两名患有CAIS的年轻中国女性因原发性闭经转介到我院。排除了睾酮（T）和双氢睾酮（DHT）合成缺陷。体格检查显示患者女性外生殖器正常，乳房发育正常，腋窝和四肢有毫毛，但无阴毛，阴道盲端。通过基因组DNA测序检测到两种不同类型的AR突变：家族A显示AR基因外显子2缺失;家族B显示AR基因外显子8的单核苷酸C至T转换，导致脯氨酸893-亮氨酸取代（Pro 893 Leu）。睾丸组织学显示生精小管发育不成熟，无生精细胞或精子。在两种情况下均未观察到AR免疫反应性。3例成年患者双侧睾丸切除后恢复良好。对家庭B的青少年患者进行随访。我们目前对这两个家族的研究揭示了两种不同类型的AR突变。AIS的明确诊断是基于临床检查和遗传学研究。我们的研究结果验证了CAIS的机制，也丰富了AR基因突变数据库。
Mutations of androgen receptor (AR) are the most frequent cause of 46, XY disorders of sex development and associated with a variety of phenotypes, ranging from phenotypic women (complete androgen insensitivity syndrome (CAIS)) to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). From 2009 to 2012, two young Chinese female individuals with CAIS from two families were referred to our hospital due to primary amenorrhea. Defects in testosterone (T) and dihydrotestosterone (DHT) synthesis were excluded. Physical examination revealed that the patients have normal female external genitalia, normal breast development, vellus hair in the axilla and on the arms and legs, but absence of pubic hair, and a blind-ending vagina. Two different types of AR mutations have been detected by sequencing of genomic DNA: Family A showed deletion of exon 2 in AR gene; Family B showed a single nucleotide C-to-T transition in exon 8 of AR gene resulting in a proline 893-to-leucine substitution (Pro893Leu). Testicular histology showed developmental immaturity of seminiferous tubules with the absence of spermatogenic cells or spermatozoa. No AR immunoreactivity was observed in either case. Three adult patients recovered well from bilateral orchiectomy. The juvenile patient of family B was followed up. Our present study on these two families revealed two different types of AR mutation. The definitive diagnosis of AIS was based on clinical examination and genetic investigations. Our findings verified the mechanism of CAIS and also enriched AR Gene Mutation Database.