Novel PMM2 missense mutation in a Chinese family with non-syndromic premature ovarian insufficiency

Purpose This study sought to identify a disease-related gene in a consanguineous Chinese family in which there were two premature ovarian insufficiency (POI) sisters. Method We used whole-exome sequencing and Sanger sequencing to identify the disease-causing gene. Results were verified using an assay of mutant protein and in silico analyses. Result We identified a novel missense mutation (NM_000303: c.556G>A, p.Gly186Arg) in the PMM2 gene. The two sisters suffer from premature ovarian insufficiency (POI) only and have no other symptoms of congenital disorder of glycosylation type-1a (CDG-Ia). We found that the enzymic activity of the mutant PMM2 protein was reduced by 55.21% (p < 0.05) when compared with wild type, and many in silico tools suggested the mutation is disease-related. Conclusion This particular gene modification results in changes in activity of phosphomannomutase modification, which could lead to PMM2-CDG-Ia with an uncommon phenotype.