Please use this identifier to cite or link to this item: http://hdl.handle.net/11452/30096
Title: Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility
Authors: Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.
0000-0002-9802-0880
Temel, Şehime
AAG-8385-2021
6507885442
Keywords: Variants
Azoospermia
Genetics & heredity
Issue Date: 15-Jun-2020
Publisher: Cell Press
Citation: Wyrwoll, M. J. vd. (2020). "Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility". American Journal of Human Genetics, 107(2), 342-351.
Abstract: Male infertility affects similar to 7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 associated protein, in three unrelated men. This variant most likely results in a truncated protein as shown in vitro by heterologous expression of mutant M1AP. Next, we screened four large cohorts of infertile men and identified three additional individuals carrying homozygous c.676dup and three carrying combinations of this and other likely causal variants in M1AP. Moreover, a homozygous missense variant, c.1166C>T (p.Pro389Leu), segregated with infertility in five men from a consanguineous Turkish family. The common phenotype between all affected men was NOA, but occasionally spermatids and rarely a few spermatozoa in the semen were observed. A similar phenotype has been described for mice with disruption of M1ap. Collectively, these findings demonstrate that mutations in M1AP are a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity.
Description: Bu çalışmada 26 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır.
URI: https://doi.org/10.1016/j.ajhg.2020.06.010
https://www.sciencedirect.com/science/article/pii/S0002929720301981
http://hdl.handle.net/11452/30096
ISSN: 0002-9297
1537-6605
Appears in Collections:PubMed
Scopus
Web of Science

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