Frameshift Mutation Identified in Premature Ovarian Failure

(HealthDay News) — A frameshift mutation in a gene encoding a cohesin subunit has been identified in a large consanguineous family with premature ovarian failure, according to a brief report published in the March 6 issue of the New England Journal of Medicine.

Sandrine Caburet, PhD, from the Université Paris Diderot, and colleagues used whole-exome sequence analysis of a large consanguineous family with inherited premature ovarian failure to examine the genetic causes of the disorder.

The researchers identified a homozygous 1-bp deletion inducing a frame shift mutation in the gene encoding stromal antigen 3 (STAG3), which encodes a subunit of cohesin. This mutation was confirmed on Sanger sequencing, and the mutation cosegregated with the premature ovarian failure phenotype. In mouse studies, female Stag3^−/− mice were sterile and their fetal oocytes were arrested at early prophase I. Histological analysis of the ovaries of Stag3^−/− mice showed a lack of oocytes at 1, 2, and 6 weeks of age.

“Our results implicate STAG3 mutation in premature ovarian failure and the meiosis-specific cohesin complexes in enabling fertility,” the authors write. “We propose that mutations affecting other meiosis-specific subunits of the cohesin complex could lead to similar functional defects and explain ovarian failure in women with premature ovarian failure.”

Full Text (subscription or payment may be required)