title: Transcription factor FIGLA is mutated in patients with premature ovarian failure.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Zhao
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
authors.forename: Yingying
authors.initials: Y
authors.lastname: Qin
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Shi
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Youngsok
authors.initials: Y
authors.lastname: Choi
authors.forename: Joe Leigh
authors.initials: JL
authors.lastname: Simpson
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Rajkovic
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D019281:Dimerization; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D009154:Mutation; D020125:Mutation, Missense; D016649:Primary Ovarian Insufficiency / Q000235:genetics* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D020798:Two-Hybrid System Techniques
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D011994:Recombinant Proteins; C109920:Figla protein, mouse; C407909:TCF3 protein, human