Mutant cohesin in premature ovarian failure.

Sandrine Caburet Valerie A Arboleda Elena Llano Paul A Overbeek Jose Luis Barbero Kazuhiro Oka Wilbur Harrison Daniel Vaiman Ziva Ben-Neriah Ignacio García-Tuñón Marc Fellous Alberto M Pendás Reiner A Veitia Eric Vilain

N Engl J Med

Institut Jacques Monod, Université Paris Diderot (S.C., M.F., R.A.V.), and Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, INSERM (D.V., M.F.) - both in Paris; the Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (V.A.A., E.V.); Departamento de Fisiología y Farmacología, Universidad de Salamanca (E.L.), and Instituto de Biología Molecular y Celular del Cáncer (E.L., I.G.-T., A.M.P.) - both in Salaman ca, Spain; the Department of Molecular Cellular Biology, Baylor College of Medicine, Houston (P.A.O., K.O., W.H.); Centro de In vestigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid (J.L.B.); and the Department of Genetics, Hadassah University Hospital, Jerusalem (Z.B.-N.).

Published: March 2014

Premature ovarian failure is a significant contributor to female infertility, with most genetic causes still unidentified.
Researchers studied a large consanguineous family and found a specific 1-bp deletion in the STAG3 gene, which is located on chromosome 7.
The STAG3 protein is vital for proper chromosome behavior during meiosis, and female mice lacking this gene are sterile due to immature oocytes being arrested at an early developmental stage.

Premature ovarian failure is a major cause of female infertility. The genetic causes of this disorder remain unknown in most patients. Using whole-exome sequence analysis of a large consanguineous family with inherited premature ovarian failure, we identified a homozygous 1-bp deletion inducing a frameshift mutation in STAG3 on chromosome 7. STAG3 encodes a meiosis-specific subunit of the cohesin ring, which ensures correct sister chromatid cohesion. Female mice devoid of Stag3 are sterile, and their fetal oocytes are arrested at early prophase I, leading to oocyte depletion at 1 week of age.

Download full-text PDF	Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068824	PMC
http://dx.doi.org/10.1056/NEJMoa1309635	DOI Listing

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