2. Academic Validation
  3. A non-sense MCM9 mutation in a familial case of primary ovarian insufficiency

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

  • Clin Genet. 2016 May;89(5):603-7. doi: 10.1111/cge.12736.
F Fauchereau 1 2,  S Shalev 3 4,  E Chervinsky 3 4,  R Beck-Fruchter 5,  B Legois 1 2,  M Fellous 6 7,  S Caburet 1 2,  R A Veitia 1 2
Affiliations

Affiliations

  • 1 Institut Jacques Monod, Paris, France.
  • 2 Department of Biology, Université Paris Diderot-Paris VII, Paris Cedex, France.
  • 3 Department of Obstetrics and Gynecology, The Rappaport Faculty of Medicine, Haifa, Israel.
  • 4 Genetic Institute, Haemek Medical Center, Afula, Israel.
  • 5 OBGYN Department, Emek Medical Center, Afula, Israel.
  • 6 Department of Genetics and Development, Institut Cochin, Paris, France.
  • 7 Faculty of Medicine, Université Paris Descartes-Paris V, Paris, France.
PMID: 26771056 DOI: 10.1111/cge.12736
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.

Keywords

MCM9; exome sequencing; infertility; primary ovarian insufficiency; reproductive medicine.

Figures