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
Margot J WyrwollFrank Tüttelmann

Abstract

Male infertility affects ∼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 mu...Continue Reading

References

Aug 2, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Nelson A ArangoPatricia K Donahoe
Jul 8, 2010·Sexual Development : Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation·S LedigP Wieacker
Jan 5, 2011·Urology·Joo Yeon LeeAshok Agarwal
Dec 28, 2012·Biology of Reproduction·Nelson Alexander ArangoPatricia K Donahoe
May 30, 2013·Nature Genetics·UNKNOWN GTEx Consortium
Jun 27, 2014·Bioinformatics·Alberto MagiTommaso Pippucci
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Mar 7, 2015·Médecine sciences : M/S·Sandrine Caburet, Éric Vilain
May 15, 2015·The New England Journal of Medicine·Alexander N YatsenkoFrank Tüttelmann
Nov 1, 2016·Nature Genetics·Amy B WilfertDonald F Conrad
Feb 17, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Moran GershoniSandra E Kleiman
Aug 4, 2018·American Journal of Human Genetics·Laura KasakMaris Laan
Dec 24, 2019·American Journal of Human Genetics·Samantha L P SchilitCynthia C Morton

❮ Previous
Next ❯

Citations

Apr 4, 2021·International Journal of Molecular Sciences·Francesca CioppiCsilla Krausz
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Lucia A Torres-FernándezWaldemar Kolanus
Aug 21, 2021·European Journal of Human Genetics : EJHG·Maram ArafatRuti Parvari
Nov 11, 2021·British Medical Bulletin·Maris LaanMargus Punab

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.