A non-sense MCM9 mutation in a familial case of primary ovarian insufficiency

Clinical Genetics
F FauchereauReiner A Veitia

Abstract

Primary ovarian insufficiency (POI) results in an early loss of ovarian function, and remains idiopathic in about 80% of cases. Here, we have performed a complete genetic study of a consanguineous family with two POI cases. Linkage analysis and homozygosity mapping identified 12 homozygous regions with linkage, totalling 84 Mb. Whole-exome sequencing of the two patients and a non-affected sister allowed us to detect a homozygous causal variant in the MCM9 gene. The variant c.1483G>T [p.E495*], confirmed using Sanger sequencing, introduced a premature stop codon in coding exon 8 and is expected to lead to the loss of a functional protein. MCM9 belongs to a complex required for DNA repair by homologous recombination, and its impairment in mouse is known to induce meiotic recombination defects and oocyte degeneration. A previous study recently described two consanguineous families in which homozygous mutations of MCM9 were responsible for POI and short stature. Interestingly, the affected sisters in the family described here had a normal height. Altogether, our results provide the confirmation of the implication of MCM9 variants in POI and expand their phenotypic spectrum.

References

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Citations

Mar 23, 2018·Human Molecular Genetics·Anlu ChenDavid A Buchner
Sep 20, 2019·Human Genetics·Xi YangYanhua Wu
Nov 27, 2019·The Journal of Clinical Endocrinology and Metabolism·Lucie RenaultIsabelle Beau
Apr 4, 2020·The Journal of Clinical Endocrinology and Metabolism·Abdelkader HeddarMicheline Misrahi
Oct 4, 2016·Endocrine Reviews·Elena J TuckerAndrew H Sinclair
Mar 30, 2017·European Journal of Endocrinology·Sandrine CaburetReiner A Veitia
Feb 10, 2018·Human Reproduction·Sunita KatariAleksandar Rajkovic
Apr 8, 2020·Molecular Genetics and Genomics : MGG·Afagh AlaviElahe Elahi
Nov 9, 2018·Journal of Assisted Reproduction and Genetics·Xiang YangAleksandar Rajkovic
Jul 8, 2020·Molecular Human Reproduction·Sylvie JaillardAndrew H Sinclair
May 10, 2020·Biomedical Journal·Reiner A Veitia
Feb 12, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hideki InnanReiner A Veitia
Feb 12, 2019·DNA Repair·Wezley C Griffin, Michael A Trakselis
Mar 26, 2021·Frontiers in Cell and Developmental Biology·Chengzi HuangYingying Qin
Jul 8, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qingling YangAaron J Hsueh
Sep 25, 2021·NPJ Genomic Medicine·Yael GoldbergStavit A Shalev

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