AMH and AMHR2 genetic variants in Chinese women with primary ovarian insufficiency and normal age at natural menopause

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.