Mutant cohesin in premature ovarian failure

N Engl J Med. 2014 Mar 6;370(10):943-949. doi: 10.1056/NEJMoa1309635.


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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics*
  • Chromosomal Proteins, Non-Histone / genetics*
  • Disease Models, Animal
  • Female
  • Humans
  • Infertility, Female / genetics
  • Mice
  • Mutation*
  • Nuclear Proteins / genetics*
  • Pedigree
  • Primary Ovarian Insufficiency / genetics*


  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Nuclear Proteins
  • STAG3 protein, human
  • Stag3 protein, mouse
  • cohesins