Qin Chunrong, Yuan Zhen, Yao Jilong, Zhu Wenjie, Wu Weiqing, Xie Jiansheng
Center for Reproductive Medicine, the Affiliated Shenzhen City Maternity and Child Healthcare Hospital of Southern Medical University, Shenzhen, China.
Center for Reproductive Medicine, the Affiliated Shenzhen City Maternity and Child Healthcare Hospital of Southern Medical University, Shenzhen, China.
Reprod Biomed Online. 2014 Sep;29(3):311-8. doi: 10.1016/j.rbmo.2014.05.003. Epub 2014 May 14.
The aim of this study was to investigate the role of the anti-Müllerian hormone (AMH) signalling pathway in the pathophysiology of idiopathic primary ovarian insufficiency (POI) and age at natural menopause (ANM) using a genetic approach. DNA sequencing was used to detect the genotype distribution and allele frequency of the genes AMH and AMH receptor II (AMHR2) in 120 cases of idiopathic POI and 120 normal-ANM women. Fourteen sequence variants of AMHR2, including 10 novel variants, were identified. Two novel exonic missense variants were p.I209N and p.L354F. The missense variant p.I209N, which is conserved in different species, was predicted to have functional and structural impacts on the AMHR2 protein. The clinical significance of one additional variant (p.L354F) remains arguable pending functional studies. The genotype frequencies of AMH and AMHR2 were similar in distribution for POI patients and normal-ANM women. These findings suggest that POI patients and normal-ANM women in China share AMH and AMHR2 genetic variants. The AMH signalling pathway associated with ANM also may contribute to POI.
本研究旨在采用遗传学方法探讨抗苗勒管激素（AMH）信号通路在特发性原发性卵巢功能不全（POI）病理生理学及自然绝经年龄（ANM）中的作用。采用DNA测序法检测120例特发性POI患者及120例正常ANM女性中AMH基因和AMH受体II（AMHR2）基因的基因型分布及等位基因频率。共鉴定出14种AMHR2序列变异，其中包括10种新变异。两个新的外显子错义变异为p.I209N和p.L354F。错义变异p.I209N在不同物种中保守，预计对AMHR2蛋白具有功能和结构影响。另一个变异（p.L354F）的临床意义有待功能研究确定。POI患者和正常ANM女性中AMH和AMHR2的基因型频率分布相似。这些发现表明，中国的POI患者和正常ANM女性共享AMH和AMHR2基因变异。与ANM相关的AMH信号通路也可能与POI有关。
