Transcription factor FIGLA is mutated in patients with premature ovarian failure.
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.
Zhao
Han
H
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
Chen
Zi-Jiang
ZJ
Qin
Yingying
Y
Shi
Yuhua
Y
Wang
Shan
S
Choi
Youngsok
Y
Simpson
Joe Leigh
JL
Rajkovic
Aleksandar
A
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
D051792:Basic Helix-Loop-Helix Proteins; D011994:Recombinant Proteins; C109920:Figla protein, mouse; C407909:TCF3 protein, human