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Mutations in MSH5 in primary ovarian insufficiency
- Source :
- Human Molecular Genetics
- Publication Year :
- 2017
- Publisher :
- Oxford University Press (OUP), 2017.
-
Abstract
- Primary ovarian insufficiency (POI) is a genetically heterogeneous disorder that occurs in familial or sporadic fashion. Through whole exome sequencing in a Chinese pedigree with POI, we identified a novel homozygous missense mutation (ENST00000375755: c.1459G > T, p.D487Y) in the MSH5 gene in two sisters with POI. The homologous mutation in mice resulted in atrophic ovaries without oocytes, and in vitro functional study revealed that mutant MSH5 impaired DNA homologous recombination repair. From sanger sequencing of MSH5 in 200 sporadic POI patients, we identified three heterozygous mutations (ENST00000375755: c.1057C > A, p.L353M; c.1459G > T, p.D487Y and c.2107 A > G, p.I703V). Considering the heterozygous p.D487Y carrier in the POI pedigree was fertile, the causality of the three heterozygous mutations in POI need more evidence. Our studies confirmed that perturbation of genes involved in DNA damage repair could lead to non-syndromic POI. The underlying mechanism-inability to repair DNA damage-will receive increasing attention with respect to POI.
- Subjects :
- Adult
Male
0301 basic medicine
Heterozygote
DNA repair
Mutation, Missense
Cell Cycle Proteins
Primary Ovarian Insufficiency
Biology
Mice
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Genetics
Animals
Humans
Missense mutation
Exome
Molecular Biology
Gene
Genetics (clinical)
Exome sequencing
Sanger sequencing
030219 obstetrics & reproductive medicine
Base Sequence
Genetic heterogeneity
Siblings
Homozygote
Articles
General Medicine
Pedigree
MSH5
030104 developmental biology
symbols
Female
Homologous recombination
Subjects
Details
- ISSN :
- 14602083 and 09646906
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Human Molecular Genetics
- Accession number :
- edsair.doi.dedup.....81787137b1c028122c499fb629f1af83