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Novel WT1 Missense Mutations in Han Chinese Women with Premature Ovarian Failure
- Source :
- Scientific Reports
- Publication Year :
- 2015
-
Abstract
- Premature ovarian failure (POF) is a heterogeneous disease. Though dozens of candidate genes have been identified for the genetic etiology of POF, it is largely unexplained in majority of patients. Recently, Wt1+/R394W mice was found to present POF-like phenotype, which indicates that WT1 might be a plausible candidate gene for non-syndromic POF. The coding region of WT1 gene was screened in 384 patients with POF and 6 novel variations were identified, including two missense mutations (p. Pro126Ser in exon1 and p. Arg370His in exon7) and four intronic variants (c.647-27C > T, c.647-13G > C, c.647-13G > A in intron1 and c.950 + 14T > C in intron 4). In vitro experiments showed that both mutant p. Pro126Ser and p. Arg370His repressed the expression of Amh and Cdh1 and induced the expression of Fshr and Cyp19 in mRNA level (P AMH, FSHR, CYP19 and CDH1) are required for granular cells (GCs) proliferation, differentiation and oocyte-GCs interaction. The novel mutant p. P126S and p. R370H in the WT1 gene potentially impaired GCs differentiation and oocyte-GCs interaction, which might result in loss of follicles prematurely. Therefore, WT1 is a plausible causal gene for POF.
- Subjects :
- Adult
Candidate gene
endocrine system
China
Genes, Wilms Tumor
endocrine system diseases
Mutant
Molecular Sequence Data
Mutation, Missense
Biology
Primary Ovarian Insufficiency
medicine.disease_cause
Polymorphism, Single Nucleotide
Article
CDH1
Andrology
Young Adult
Asian People
Gene Order
medicine
Missense mutation
Humans
Genetic Predisposition to Disease
Amino Acid Sequence
Gene
Genetics
Mutation
Multidisciplinary
Granulosa Cells
urogenital system
medicine.disease
Phenotype
female genital diseases and pregnancy complications
Introns
Premature ovarian failure
Genetic Loci
biology.protein
Female
RNA Splice Sites
Sequence Alignment
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....9bcb35ac9d8ac28f9950073d9f51f90b