A novel heterozygous splice-altering mutation in HFM1 may be a cause of premature ovarian insufficiency

Abstract

Abstract Background Premature ovarian insufficiency (POI) leads to early loss of ovarian function in women aged A) associated with POI was identified by whole-exome sequencing. This mutation was heterozygous in the affected family members and was absent in the unaffected family members. In silico analysis predicted that the mutation was potentially pathogenic. Bioinformatic splice prediction tools revealed that the mutation was very likely to have a strong impact on splice site function. Results of the minigene assay revealed that the mutation changed the mRNA splicing repertory. Conclusions The missense mutation of the HFM1 gene (c.3470G > A) may be a cause of POI. The mutation altered mRNA splicing in cells. This study can provide geneticists with deeper insight into the pathogenesis of POI and aid clinicians in making early diagnoses in affected women.

Keywords

• Premature ovarian insufficiency
• HFM1
• Whole-exome sequencing
• Splicing minigene