ArticleReproductive biology and endocrinology : RB&E2022
Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia.
Article in Reproductive biology and endocrinology : RB&E, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- The role of DNA mismatch repair mutS/mutL homolog genes in spermatogenesis and male infertility: a systematic review and cohort study.Reproductive biology and endocrinology : RB&E · 2025Pooled it
- Diagnostic yield of exome sequencing in nonobstructive azoospermia (NOA): A systematic review and meta-analysis.PloS one · 2025Pooled it
- Variants in ZZS Complex-Associated Genes TEX11 and M1AP Are Responsible for Male Infertility and Nonobstructive Azoospermia.Andrology · 2026Article
- Compound heterozygous REC114 variants in dizygotic twins causes meiotic arrest and non-obstructive azoospermia.Basic and clinical andrology · 2025Article
- Bi-allelic KCTD19 variants associated with meiotic arrest and non-obstructive azoospermia in humans.Journal of human genetics · 2025Article
- Genetic and functional analysis reveals novel mutations in meiotic genes underlying non-obstructive azoospermia.Journal of assisted reproduction and genetics · 2025Article
- High-resolution optical genome mapping unveils gene disruptions in a reciprocal chromosomal translocation and severe male infertility: a case report.Journal of assisted reproduction and genetics · 2025Article
- Genetic insights into non-obstructive azoospermia: Implications for diagnosis and TESE outcomes.Journal of assisted reproduction and genetics · 2025Article
- Novel biallelic MCMDC2 variants were associated with meiotic arrest and nonobstructive azoospermia.Asian journal of andrology · 2025Article
- IGF2BP1/HMOX1 Mediates Fate Determinations of Human Spermatogonial Stem Cells and Male Infertility via an m6A-Dependent Manner.Research (Washington, D.C.) · 2025Article
- Whole exome sequencing analysis of 167 men with primary infertility.BMC medical genomics · 2024Article
- Splicing Mutation in DNALI1 Causes Male Infertility with Severe Oligoasthenoteratozoospermia in Humans.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Conserved genes regulating human sex differentiation, gametogenesis and fertilization.Journal of translational medicine · 2024Review
- A novel homozygote nonsense variant of MSH4 leads to primary ovarian insufficiency and non-obstructive azoospermia.Molecular biology reports · 2024Article
- Review
- Bi-allelic MEI1 variants cause meiosis arrest and non-obstructive azoospermia.Journal of human genetics · 2023Article
- Multi-omic analysis in normal colon organoids highlights MSH4 as a novel marker of defective mismatch repair in Lynch syndrome and microsatellite instability.Cancer medicine · 2023Article
- Genetic variants underlying spermatogenic arrests in men with non-obstructive azoospermia.Cell cycle (Georgetown, Tex.) · 2023Article
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNon-obstructive azoospermia (NOA) is one of the most severe type in male infertility, and the genetic causes of NOA with meiotic arrest remain elusive.
methodsFour Chinese families with NOA participated in the study. We performed whole-exome sequencing (WES) for the four NOA-affected patients in four pedigrees. The candidate causative gene was further verified by Sanger sequencing. Hematoxylin and eosin staining (H&E) and immunohistochemistry (IHC) were carried out to evaluate the stage of spermatogenesis arrested in the patients with NOA.
resultsWe identified two novel homozygous frameshift mutations of MSH4 and two novel compound heterozygous variants in MSH4 in four pedigrees with NOA. Homozygous loss of function (LoF) variants in MSH4 was identified in the NOA-affected patient (P9359) in a consanguineous Chinese family (NM_002440.4: c.805_812del: p.V269Qfs*15) and one patient with NOA (P21504) in another Chinese family (NM_002440.4: c.2220_2223del:p.K741Rfs*2). Also, compound heterozygous variants in MSH4 were identified in two NOA-affected siblings (P9517 and P9517B) (NM_002440.4: c.G1950A: p.W650X and c.2179delG: p.D727Mfs*11), and the patient with NOA (P9540) (NM_002440.4: c.G244A: p.G82S and c.670delT: p.L224Cfs*3). Histological analysis demonstrated lack of spermatozoa in seminiferous tubules of all patients and IHC showed the spermatogenesis arrested at the meiotic prophase I stage. Consistent with the autosomal recessive mode of inheritance, all of these mutations were inherited from heterozygous parental carriers.
conclusionsWe identified that six novel mutations in MSH4 responsible for meiotic arrest and NOA. And these results provide researchers with a new insight to understand the genetic etiology of NOA and to identify new loci for genetic counselling of NOA.
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