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
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adult
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Amino Acid Sequence
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Asian People / genetics
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Base Sequence
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Basic Helix-Loop-Helix Transcription Factors / chemistry
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Basic Helix-Loop-Helix Transcription Factors / genetics*
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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DNA Mutational Analysis
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Dimerization
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Female
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Frameshift Mutation
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Humans
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Mutation*
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Mutation, Missense
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Primary Ovarian Insufficiency / genetics*
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Primary Ovarian Insufficiency / metabolism
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Protein Structure, Quaternary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Deletion
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Two-Hybrid System Techniques
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Figla protein, mouse
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Recombinant Proteins
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TCF3 protein, human