Transcription factor FIGLA is mutated in patients with premature ovarian failure

Am J Hum Genet. 2008 Jun;82(6):1342-8. doi: 10.1016/j.ajhg.2008.04.018. Epub 2008 May 22.

Abstract

Premature Ovarian Failure (POF) is a genetically heterogenous disorder that leads to hypergonadotropic ovarian failure and infertility. We screened 100 Chinese women with POF for mutations in the oocyte-specific gene FIGLA and identified three variants in four women: missense mutation c.11C --> A (p.A4E) was found in two women; deletion c. 15-36 del (p.G6fsX66), resulting in a frameshift that leads to haploinsufficiency, was found in one woman; and deletion c.419-421 delACA (p.140 delN) was found in one. Functional analyses by the yeast two-hybrid assay demonstrated that the p.140 delN mutation disrupted FIGLA binding to the TCF3 helix-loop-helix (HLH) domain. Our findings show that a subset of Chinese women with sporadic, premature ovarian failure harbor mutations in FIGLA.

Publication types

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

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Asian Continental Ancestry Group / genetics
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • DNA Mutational Analysis
  • Dimerization
  • Female
  • Frameshift Mutation
  • Humans
  • Mutation*
  • Mutation, Missense
  • Primary Ovarian Insufficiency / genetics*
  • Primary Ovarian Insufficiency / metabolism
  • Protein Structure, Quaternary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Two-Hybrid System Techniques

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Figla protein, mouse
  • Recombinant Proteins
  • TCF3 protein, human