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Comparative functional analysis of two fibroblast growth factor receptor 1 (FGFR1) mutations affecting the same residue (R254W and R254Q) in isolated hypogonadotropic hypogonadism (IHH)
- Source :
- Gene
- Publication Year :
- 2013
-
Abstract
- FGFR1 mutations have been identified in both Kallmann syndrome and normosmic HH (nIHH). To date, few mutations in the FGFR1 gene have been structurally or functionally characterized in vitro to identify molecular mechanisms that contribute to the disease pathogenesis. We attempted to define the in vitro functionality of two FGFR1 mutants (R254W and R254Q), resulting from two different amino acid substitutions of the same residue, and to correlate the in vitro findings to the patient phenotypes. Two unrelated GnRH deficient probands were found to harbor mutations in FGFR1 (R254W and R254Q). Mutant signaling activity and expression levels were evaluated in vitro and compared to a wild type (WT) receptor. Signaling activity was determined by a FGF2/FGFR1 dependent transcription reporter assay. Receptor total expression levels were assessed by Western blot and cell surface expression was measured by a radiolabeled antibody binding assay. The R254W maximal receptor signaling capacity was reduced by 45% (p
- Subjects :
- Male
Isolated hypogonadotropic hypogonadism
medicine.medical_specialty
Adolescent
Genotype
Glycoside Hydrolases
Mutant
030209 endocrinology & metabolism
Biology
Gonadotropin-Releasing Hormone
03 medical and health sciences
0302 clinical medicine
Internal medicine
Chlorocebus aethiops
Genetics
medicine
Animals
Humans
Computer Simulation
Receptor, Fibroblast Growth Factor, Type 1
Receptor
Protein maturation
030304 developmental biology
Regulation of gene expression
0303 health sciences
Hypogonadism
Fibroblast growth factor receptor 1
Wild type
Kallmann Syndrome
General Medicine
medicine.disease
Phenotype
Endocrinology
Gene Expression Regulation
COS Cells
Mutation
Signal transduction
Signal Transduction
Subjects
Details
- Volume :
- 516
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Gene
- Accession number :
- edsair.doi.dedup.....4bc3901c73bb5c2923d6d5265592299b