Two newly identified mutations in HFM1 may contribute to premature ovarian insufficiency

Abstract

BACKGROUND: Premature ovarian insufficiency (POI) occurs in about 1% of women under the age of 40. It means a woman’s ovarian function declines or even ceases, causing a decline in her fertility. In most women with POI, the genetic cause of this disease is not known. METHODS: We used whole-exome sequencing (WES) to analyze the genetic factors of members of the POI family, and we selected two Chinese Han families with POI as experimental subjects. Sanger sequencing confirmed the existence of gene mutations in these two families, and the protein function was predicted by three online protein-prediction websites: SIFT, PolyPhen-2, and Mutation Taster. RESULTS: Through WES and Sanger sequencing, two novel heterozygous missense mutations (c.1209G>C, p. Gln403His and c.1477A>C, p. Lys493Gln) of HFM1 related to POI were identified. This mutation is heterozygous in patients, but there is no missense mutation in unaffected family members. Three online protein-prediction programs, SIFT, PolyPhen-2, and Mutation Taster, were used to predict protein function, and they showed that this kind of mutation is harmful to protein structure and function. CONCLUSIONS: Two new missense mutations (c.1209G>C, p. Gln403His and c.1477A>C, p.Lys493Gln) detected in the HFM1 gene may cause POI. This research can provide geneticists with a deeper understanding of the pathogenesis of POI, and it can also help clinicians make early diagnoses of affected women of childbearing age. (Am J Transl Med 2021. 5:147-153).