Journal
MOLECULAR HUMAN REPRODUCTION
Volume 26, Issue 9, Pages 665-677Publisher
OXFORD UNIV PRESS
DOI: 10.1093/molehr/gaaa050
Keywords
premature ovarian insufficiency; non-obstructive azoospermia; whole-exome sequencing; STAG3
Funding
- CHU Rennes and Rennes 1 University, Faculty of Medicine in France
- Peter Doherty Early Career Fellowship [1054432]
- National Health and Medical Research Council [1074258]
- Australian National Health and Medical Research Council [1062854]
- Victorian Government's Operational Infrastructure Support Program
- European Society of Pediatric Endocrinology
- Agence Nationale de la Recherche (ANR) [ANR-10-LABX-73 REVIVE, ANR-17-CE14-0038-01]
- Agence Nationale de la Recherche (ANR) [ANR-17-CE14-0038] Funding Source: Agence Nationale de la Recherche (ANR)
- National Health and Medical Research Council of Australia [1074258] Funding Source: NHMRC
Ask authors/readers for more resources
Infertility, a global problem affecting up to 15% of couples, can have varied causes ranging from natural ageing to the pathological development or function of the reproductive organs. One form of female infertility is premature ovarian insufficiency (POI), affecting up to 1 in 100 women and characterised by amenorrhoea and elevated FSH before the age of 40. POI can have a genetic basis, with over 50 causative genes identified. Non-obstructive azoospermia (NOA), a form of male infertility characterised by the absence of sperm in semen, has an incidence of 1% and is similarly heterogeneous. The genetic basis of male and female infertility is poorly understood with the majority of cases having no known cause. Here, we study a case of familial infertility including a proband with POI and her brother with NOA. We performed whole-exome sequencing (WES) and identified a homozygous STAG3 missense variant that segregated with infertility. STAG3 encodes a component of the meiosis cohesin complex required for sister chromatid separation. We report the first pathogenic homozygous missense variant in STAG3 and the first STAG3 variant associated with both male and female infertility. We also demonstrate limitations of WES for the analysis of homologous DNA sequences, with this variant being ambiguous or missed by independent WES protocols and its homozygosity only being established via long-range nested PCR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available