Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Novel Inactivating Mutations of the DCAF17 gene in American and Turkish families cause male infertility and female subfertility in the mouse model. Gurbuz F et al. (2017) Loss of function DCAF17 variants cause hypogonadism, partial alopecia, diabetes mellitus, mental retardation, and deafness with variable clinical presentation ranging. DCAF17 pathogenic variants have been largely reported in the Middle Eastern populations, but the incidence in American families is rare and animal models are lacking. Exome sequencing in five women with syndromic hypergonadotropic hypogonadism from two unrelated families revealed novel pathogenic variants in the DCAF17 gene. DCAF17 exon 2 (c.127-1G>C) novel homozygous variants were discovered in four Turkish siblings, while one American was compound heterozygous for one stop gain variant in exon 5 (c.C535T; p.Gln179*) and previously described stop gain variant in exon 9 (c.G906A; p.Trp302*). A mouse model mimicking loss of function in exon 2 of Dcaf17 was generated using CRISPR/Cas9 and showed female subfertility and male infertility. Our results identify two novel variants, and show that Dcaf17 plays a significant role in mammalian gonadal development and infertility.//////////////////