STAG3 homozygous missense variant causes primary ovarian insufficiency and male non-obstructive azoospermia

29Citations
Citations of this article
28Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

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.

Cite

CITATION STYLE

APA

Jaillard, S., McElreavy, K., Robevska, G., Akloul, L., Ghieh, F., Sreenivasan, R., … Sinclair, A. H. (2020). STAG3 homozygous missense variant causes primary ovarian insufficiency and male non-obstructive azoospermia. Molecular Human Reproduction, 26(9), 665–677. https://doi.org/10.1093/molehr/gaaa050

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free