A novel missense variant of LAMC1 as a possible cause of premature ovarian insufficiency in a Chinese family

Abstract Background: Premature ovarian insufficiency (POI) results in the loss of ovarian function and reproductive impairment. The cause of most cases of POI is unclear, although genetic factors are thought to be involved. This study aimed to identify novel pathogenic genes and variants in a Chinese family with POI.Results: An assessment of the family pedigree suggested that POI was inherited in an autosomal dominant manner in this family. Whole-exome sequencing of the proband and her affected mother identified a novel heterozygous missense variant in the laminin subunit gamma-1 gene (LAMC1; NM_002293.4:c.A3281T:p.D1094V). This variant was not found in any public databases, and was highly conserved among mammals. Online software predicted it to be deleterious with respect to protein function. Its presence in the POI family was confirmed by Sanger sequencing.Conclusions: We report a novel heterozygous missense variant in LAMC1 in a Chinese POI family, which was inherited in an autosomal dominant manner. This variant may result in the development of POI. Our results provide supporting evidence for a causative role for LAMC1 variants in POI.