ArticleEuropean journal of human genetics : EJHG2021
Pathogenic variations in Germ Cell Nuclear Acidic Peptidase (GCNA) are associated with human male infertility.
Article in European journal of human genetics : EJHG, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- A novel loss-of-function mutation in MCMDC2 is associated with male infertility.Human genome variation · 2026Article
- Epigenetic regulation by DNA methylation, histone modifications and chromatin remodeling complexes in controlling spermatogenesis and their dysfunction with male infertility.Cellular and molecular life sciences : CMLS · 2025Review
- Orchiopexy: one procedure, two diagnoses - different male infertility outcomes.Asian journal of andrology · 2024Article
- Review
- Zebrafish as a model system for studying reproductive diseases.Frontiers in cell and developmental biology · 2024Review
- A pathogenic variant in the uncharacterizedHGG advances · 2023Article
- GCNA is a histone binding protein required for spermatogonial stem cell maintenance.Nucleic acids research · 2023Article
- Large-scale analyses of the X chromosome in 2,354 infertile men discover recurrently affected genes associated with spermatogenic failure.American journal of human genetics · 2022Article
- ExAgBov: A public database of annotated variations from hundreds of bovine whole-exome sequencing samples.Scientific data · 2022Article
- Article
- Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia.American journal of human genetics · 2022Article
- Proteolysis in Reproduction: Lessons From Gene-Modified Organism Studies.Frontiers in endocrinology · 2022Review
- Genomics elucidates both common and rare disease aetiology.European journal of human genetics : EJHG · 2021Article
- Biallelic mutations inAsian journal of andrologyArticle
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infertility affects one in six couples, half of which are caused by a male factor. Male infertility can be caused by both, qualitative and quantitative defects, leading to Oligo- astheno-terato-zoospermia (OAT; impairment in ejaculate sperm cell concentration, motility and morphology). Azoospermia defined as complete absence of sperm cells in the ejaculation. While hundreds of genes are involved in spermatogenesis the genetic etiology of men's infertility remains incomplete.We identified a hemizygous stop gain pathogenic variation (PV) in the X-linked Germ Cell Nuclear Acidic Peptidase (GCNA), in an Azoospermic patient by exome sequencing. Assessment of the prevalence of pathogenic variations in this gene in infertile males by exome sequence data of 11 additional unrelated patients identified a probable hemizygous causative missense PV in GCNA in a severe OAT patient. Expression of GCNA in the patients' testes biopsies and the stage of spermatogonial developmental arrest were determined by immunofluorescence and immunohistochemistry. The Azoospermic patient presented spermatogenic maturation arrest with an almost complete absence of early and late primary spermatocytes and thus the complete absence of sperm. GCNA is critical for genome integrity and its loss results in genomic instability and infertility in Drosophila, C. elegans, zebrafish, and mouse. PVs in GCNA appear to be incompatible with male fertility in humans as well: A stop-gain PV caused Azoospermia and a missense PV caused severe OAT with very low fertilization rates and no pregnancy in numerous IVF treatments.
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