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A novel homozygous mutation in the FSHR gene is causative for primary ovarian insufficiency
- Source :
- Fertility and sterility. 108(6)
- Publication Year :
- 2017
-
Abstract
- Objective To identify the potential FSHR mutation in a Chinese woman with primary ovarian insufficiency (POI). Design Genetic and functional studies. Setting University-based reproductive medicine center. Patient(s) A POI patient, her family members, and another 192 control women with regular menstruation. Intervention(s) Ovarian biopsy was performed in the patient. Sanger sequencing was carried out for the patient, her sister, and parents. The novel variant identified was further confirmed with the use of control subjects. Main Outcome Measure(s) Sanger sequencing and genotype analysis to identify the potential variant of the FSHR gene; hematoxylin and eosin staining of the ovarian section to observe the follicular development; Western blotting and immunofluorescence to detect FSH receptor (FSHR) expression; and cyclic adenosine monophosphate (cAMP) assay to monitor FSH-induced signaling. Result(s) Histologic examination of the ovaries in the patient revealed follicular development up to the early antral stage. Mutational screening and genotype analysis of the FSHR gene identified a novel homozygous mutation c.175C>T (p.R59X) in exon 2, which was inherited in the autosomal recessive mode from her heterozygous parents but was absent in her sister and the 192 control women. Functional studies demonstrated that in vitro the nonsense mutation caused the loss of full-length FSHR expression and that p.R59X mutant showed no response to FSH stimulation in the cAMP level. Conclusion(s) The mutation p.R59X in FSHR is causative for POI by means of arresting folliculogenesis.
- Subjects :
- 0301 basic medicine
Adult
endocrine system
medicine.medical_specialty
Biopsy
Nonsense mutation
DNA Mutational Analysis
Ovary
Biology
Primary Ovarian Insufficiency
medicine.disease_cause
Transfection
03 medical and health sciences
symbols.namesake
Exon
0302 clinical medicine
Ovarian Follicle
Risk Factors
Internal medicine
Follicular phase
medicine
Cyclic AMP
Humans
Genetic Predisposition to Disease
Genetic Association Studies
Sanger sequencing
Mutation
030219 obstetrics & reproductive medicine
Homozygote
Obstetrics and Gynecology
Pedigree
030104 developmental biology
Endocrinology
medicine.anatomical_structure
HEK293 Cells
Phenotype
Reproductive Medicine
Codon, Nonsense
Case-Control Studies
symbols
Receptors, FSH
Female
Folliculogenesis
Follicle-stimulating hormone receptor
Subjects
Details
- ISSN :
- 15565653
- Volume :
- 108
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Fertility and sterility
- Accession number :
- edsair.doi.dedup.....847278481a3f473980730577d5d20079