• PMID: 29178422
• Gene Name: DCAF17
• Condition: Male infertility
• Association: Associated
• Mutation: exon 2 (c.127-1G > C), exon 5 (c.C535T; p.Gln179*), exon 9 (c.G906A; p.Trp302*)
• Population size: 9
• Population details: 9 cases
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

Novel inactivating mutations of the DCAF17 gene in American and Turkish families cause male infertility and female subfertility in the mouse model

Gurbuz F, Desai S, Diao F, Turkkahraman D, Wranitz F, Wood-Trageser M, Shin YH, Kotan LD, Jiang H, Witchel S, Gurtunca N, Yatsenko S, Mysliwec D, Topaloglu K, Rajkovic A.

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 the DCAF17 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 of Dcaf17 was generated using CRISPR/Cas9 and showed female subfertility and male infertility. Our results identify 2 novel variants, and show that Dcaf17 plays a significant role in mammalian gonadal development and infertility. CI - © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Gurbuz, F AU - Gurbuz F AD - Division of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, Adana, Turkey. FAU - Desai, S AU - Desai S AD - Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Diao, F AU - Diao F AD - Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania. AD - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. FAU - Turkkahraman, D AU - Turkkahraman D AD - Division of Pediatric Endocrinology, Antalya Training and Research Hospital, Antalya, Turkey. FAU - Wranitz, F AU - Wranitz F AD - Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Wood-Trageser, M AU - Wood-Trageser M AD - Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Shin, Y-H AU - Shin YH AD - Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Kotan, L D AU - Kotan LD AD - Department of Biotechnology, Institute of Sciences, Cukurova University, Adana, Turkey. FAU - Jiang, H AU - Jiang H AD - Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Witchel, S AU - Witchel S AD - Division of Pediatric Endocrinology, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Gurtunca, N AU - Gurtunca N AD - Division of Pediatric Endocrinology, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Yatsenko, S AU - Yatsenko S AUID- ORCID: 0000-0003-4809-8601 AD - Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania. AD - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. AD - Department of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania. FAU - Mysliwec, D AU - Mysliwec D AD - Division of Pediatric Endocrinology, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Topaloglu, K AU - Topaloglu K AD - Division of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, Adana, Turkey.