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Pathogenic variations in Germ Cell Nuclear Acidic Peptidase (GCNA) are associated with human male infertility
Year:
2021
Source of publication :
European Journal of Human Genetics
Authors :
Gershoni, Moran
;
.
Volume :
29
Co-Authors:

Maram Arafat 
Sandra E Kleiman 
 Ali AbuMadighem
Atif Zeadna 
Eliahu Levitas
Iris Har Vardi
Shimi Barda 
Ofer Lehavi
Ron Hauser
Eitan Lunenfeld
Mahmoud Huleihel
Moran Gershoni 
Ruti Parvari 

 

Facilitators :
From page:
1781
To page:
1788
(
Total pages:
8
)
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.

Note:
Related Files :
Germ Cell Nuclear Acidic Peptidase (GCNA)
human
male infertility
Show More
Related Content
More details
DOI :
10.1038/s41431-021-00946-2
Article number:
0
Affiliations:
Database:
PubMed
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
56070
Last updated date:
04/04/2022 11:47
Creation date:
25/08/2021 13:30
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Scientific Publication
Pathogenic variations in Germ Cell Nuclear Acidic Peptidase (GCNA) are associated with human male infertility
29

Maram Arafat 
Sandra E Kleiman 
 Ali AbuMadighem
Atif Zeadna 
Eliahu Levitas
Iris Har Vardi
Shimi Barda 
Ofer Lehavi
Ron Hauser
Eitan Lunenfeld
Mahmoud Huleihel
Moran Gershoni 
Ruti Parvari 

 

Pathogenic variations in Germ Cell Nuclear Acidic Peptidase (GCNA) are associated with human male infertility

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.

Scientific Publication
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