1. Novel inactivating mutations of the DCAF17 gene in American and Turkish families cause male infertility and female subfertility in the mouse model.
- Author
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Gurbuz, F., Desai, S., Diao, F., Turkkahraman, D., Wranitz, F., Wood‐trageser, M., Shin, Y.‐h., Kotan, L. D., Jiang, H., Witchel, S., Gurtunca, N., Yatsenko, S., Mysliwec, D., Topaloglu, K., and Rajkovic, A.
- Subjects
MALE infertility ,GENETIC mutation ,HYPOGONADISM ,EXONS (Genetics) ,GONADAL diseases ,DISEASE risk factors ,RISK factors in infertility - Abstract
Loss‐of‐function
DCAF17 variants cause hypogonadism, partial alopecia, diabetes mellitus, mental retardation, and deafness with variable clinical presentation.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 5 women with syndromic hypergonadotropic hypogonadism from 2 unrelated families revealed novel pathogenic variants in theDCAF17 gene.DCAF17 exon 2 (c.127‐1G > C) novel homozygous variants were discovered in 4 Turkish siblings, while 1 American was compound heterozygous for 1‐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 ofDcaf17 was generated using CRISPR/Cas9 and showed female subfertility and male infertility. Our results identify 2 novel variants, and show thatDcaf17 plays a significant role in mammalian gonadal development and infertility. [ABSTRACT FROM AUTHOR]- Published
- 2018
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