1. Rare Dysplasia from a Synonymous Mutation in FGFR3 is Indistinguishable from Wild Type by Coding Sequence Analysis
- Author
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Geller, Stephen
- Subjects
Biochemistry - Abstract
Fibroblast Growth Factor Receptor Three (FGFR3) is a receptor tyrosine kinase (RTK) and plays an important role in cellular processes such as cell proliferation, angiogenesis, differentiation, wound healing, and bone growth. FGFR3 mutations can lead to abnormal signaling often causing a bone dysplasia related disease. This study characterizes a synonymous mutation found in a patient with extreme short stature using in vitro transfections of the cDNA. The synonymous mutation (F704F) was unable to transform NIH3T3 cells. HEK293T cells transfected with the synonymous mutation showed no differences of expression, phosphorylation of the activation loop, or phosphorylation of downstream signals commonly found in cell proliferation, PLCG and Mapk. The synonymous mutation also showed no aberrant tyrosine phosphorylation when compared to the wild-type receptor. Partial Tryptic digestion and Liquid Chromatography Tandem Mass Spectroscopy showed no sequential differences between the amino acid sequences of the protein with or without the synonymous mutation. This suggests that future analysis must be done on the whole genomic sequence of FGFR3.
- Published
- 2024