[en] 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.
Disciplines :
Endocrinology, metabolism & nutrition Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
NECHIFOR - POTORAC, Iulia ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'endocrinologie clinique
Laterre, Marie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Malaise, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > > Service de rhumatologie
NECHIFOR, Vlad Andrei ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'urologie
Fasquelle, Corinne ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Colleye, Orphal ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anatomie et cytologie pathologiques
Detrembleur, Nancy ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anatomie et cytologie pathologiques
Verdin, Hannah
Symoens, Sofie
De Baere, Elfride
Daly, Adrian ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'endocrinologie clinique
Bours, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Pétrossians, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'endocrinologie clinique
Pintiaux, Axelle ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gynécologie-obstétrique
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