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The Role of MCM9 in the Etiology of Sertoli Cell-Only Syndrome and Premature Ovarian Insufficiency

Infertility in couples is a common problem, with both female and male factors contributing to similar extents. Severe, congenital disorders affecting fertility are, however, rare. While folliculogenesis and spermatogenesis are generally orchestrated via different mechanisms, some genetic anomalies c...

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Autores principales: Potorac, Iulia, Laterre, Marie, Malaise, Olivier, Nechifor, Vlad, Fasquelle, Corinne, Colleye, Orphal, Detrembleur, Nancy, Verdin, Hannah, Symoens, Sofie, De Baere, Elfride, Daly, Adrian F., Bours, Vincent, Pétrossians, Patrick, Pintiaux, Axelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917496/
https://www.ncbi.nlm.nih.gov/pubmed/36769638
http://dx.doi.org/10.3390/jcm12030990
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author Potorac, Iulia
Laterre, Marie
Malaise, Olivier
Nechifor, Vlad
Fasquelle, Corinne
Colleye, Orphal
Detrembleur, Nancy
Verdin, Hannah
Symoens, Sofie
De Baere, Elfride
Daly, Adrian F.
Bours, Vincent
Pétrossians, Patrick
Pintiaux, Axelle
author_facet Potorac, Iulia
Laterre, Marie
Malaise, Olivier
Nechifor, Vlad
Fasquelle, Corinne
Colleye, Orphal
Detrembleur, Nancy
Verdin, Hannah
Symoens, Sofie
De Baere, Elfride
Daly, Adrian F.
Bours, Vincent
Pétrossians, Patrick
Pintiaux, Axelle
author_sort Potorac, Iulia
collection PubMed
description Infertility in couples is a common problem, with both female and male factors contributing to similar extents. Severe, congenital disorders affecting fertility are, however, rare. While folliculogenesis and spermatogenesis are generally orchestrated via different mechanisms, some genetic anomalies can impair both female and male gametogenesis. Minichromosome maintenance complex component 9 (MCM9) is involved in DNA repair and mutations of the MCM9 gene have been previously reported in females with premature ovarian insufficiency (POI). MCM9 is also an emerging cancer risk gene. We performed next-generation and Sanger sequencing of fertility and related genes and hormonal and imaging studies in a kindred whose members had POI and disordered spermatogenesis. We identified a homozygous pathogenic MCM9 variant, c.394C>T (p.Arg132*) in three sisters affected by POI due to ovarian dysgenesis and their brother who had normal pubertal development but suffered from non-obstructive azoospermia. Testicular biopsy revealed Sertoli cell-only testicular histopathology. No evidence of early onset cancer was found in the homozygotic family members, but they were all young (<30 years) at the time of the study. In the male patient the homozygous MCM9 variant led to normal pubertal development and hormonal levels but caused a Sertoli-cell-only syndrome with non-obstructive azoospermia. In the homozygous females studied, the clinical, hormonal, and gonadal phenotypes revealed ovarian dysgenesis consistent with previous reports. Active screening for potential colorectal and other cancer risks in the homozygotic MCM9 subjects has been instigated.
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spelling pubmed-99174962023-02-11 The Role of MCM9 in the Etiology of Sertoli Cell-Only Syndrome and Premature Ovarian Insufficiency Potorac, Iulia Laterre, Marie Malaise, Olivier Nechifor, Vlad Fasquelle, Corinne Colleye, Orphal Detrembleur, Nancy Verdin, Hannah Symoens, Sofie De Baere, Elfride Daly, Adrian F. Bours, Vincent Pétrossians, Patrick Pintiaux, Axelle J Clin Med Article Infertility in couples is a common problem, with both female and male factors contributing to similar extents. Severe, congenital disorders affecting fertility are, however, rare. While folliculogenesis and spermatogenesis are generally orchestrated via different mechanisms, some genetic anomalies can impair both female and male gametogenesis. Minichromosome maintenance complex component 9 (MCM9) is involved in DNA repair and mutations of the MCM9 gene have been previously reported in females with premature ovarian insufficiency (POI). MCM9 is also an emerging cancer risk gene. We performed next-generation and Sanger sequencing of fertility and related genes and hormonal and imaging studies in a kindred whose members had POI and disordered spermatogenesis. We identified a homozygous pathogenic MCM9 variant, c.394C>T (p.Arg132*) in three sisters affected by POI due to ovarian dysgenesis and their brother who had normal pubertal development but suffered from non-obstructive azoospermia. Testicular biopsy revealed Sertoli cell-only testicular histopathology. No evidence of early onset cancer was found in the homozygotic family members, but they were all young (<30 years) at the time of the study. In the male patient the homozygous MCM9 variant led to normal pubertal development and hormonal levels but caused a Sertoli-cell-only syndrome with non-obstructive azoospermia. In the homozygous females studied, the clinical, hormonal, and gonadal phenotypes revealed ovarian dysgenesis consistent with previous reports. Active screening for potential colorectal and other cancer risks in the homozygotic MCM9 subjects has been instigated. MDPI 2023-01-28 /pmc/articles/PMC9917496/ /pubmed/36769638 http://dx.doi.org/10.3390/jcm12030990 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Potorac, Iulia
Laterre, Marie
Malaise, Olivier
Nechifor, Vlad
Fasquelle, Corinne
Colleye, Orphal
Detrembleur, Nancy
Verdin, Hannah
Symoens, Sofie
De Baere, Elfride
Daly, Adrian F.
Bours, Vincent
Pétrossians, Patrick
Pintiaux, Axelle
The Role of MCM9 in the Etiology of Sertoli Cell-Only Syndrome and Premature Ovarian Insufficiency
title The Role of MCM9 in the Etiology of Sertoli Cell-Only Syndrome and Premature Ovarian Insufficiency
title_full The Role of MCM9 in the Etiology of Sertoli Cell-Only Syndrome and Premature Ovarian Insufficiency
title_fullStr The Role of MCM9 in the Etiology of Sertoli Cell-Only Syndrome and Premature Ovarian Insufficiency
title_full_unstemmed The Role of MCM9 in the Etiology of Sertoli Cell-Only Syndrome and Premature Ovarian Insufficiency
title_short The Role of MCM9 in the Etiology of Sertoli Cell-Only Syndrome and Premature Ovarian Insufficiency
title_sort role of mcm9 in the etiology of sertoli cell-only syndrome and premature ovarian insufficiency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917496/
https://www.ncbi.nlm.nih.gov/pubmed/36769638
http://dx.doi.org/10.3390/jcm12030990
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