Abstract
Premature ovarian insufficiency (POI) is characterized by amenorrhea and elevated levels of follicle-stimulating hormone (FSH, usually > 25 IU/L) before 40 years of age. To identify the relationship between FSHR mutations and sporadic POI patients of Han Chinese descent, we performed Sanger sequencing of FSHR gene in 192 sporadic POI patients and 192 matched controls of Han Chinese descent. Two heterozygous missense variants, c.793A > G (p.M265V) and c.1789C > A (p.L597I), were identified exclusively in POI patients. Functional studies showed that both mutants were expressed on the cell surface, while p.L597I showed decreased membrane localization compared with wild-type FSHR. Moreover, FSH-induced cAMP production and ERK1/2 phosphorylation were reduced in the cells transfected with p.L597I mutant, but not in the cells transfected with p.M265V mutant. In addition, two single-nucleotide polymorphisms (SNPs), rs1394205 (c.-29G > A) and rs140106399 (c.*111 T > C), were identified in both POI group and control group with significantly different genotypic and allelic distributions. These results indicated that dysfunctional FSHR due to mutation or SNPs might explain a fraction of sporadic POI cases in Han Chinese population.