Achondroplasia is defined by recurrent G380R mutations of FGFR3
- Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)
- Univ. of Texas Medical School, Houston, TX (United States)
- Shriners Hospital for Crippled Children, Portland, OR (United States)
- Helsinki Univ. Hospital (Finland)
Genomic DNA from 154 unrelated individuals with achondroplasia was evaluated for mutations in the fibroblast growth factor receptor 3 (FGFR3) transmembrane domain. All but one, an atypical case, were found to have a glycine-to-arginine substitution at codon 380. Of these, 150 had a G-to-A transition at nt 1138, and 3 had a G-to-C transversion at this same position. On the basis of estimates of the prevalence of achondroplasia, the mutation rate at the FGFR3 1138 guanosine nucleotide is two to three orders of magnitude higher than that previously reported for transversions and transitions in CpG dinucleotides. To date, this represents the most mutable single nucleotide reported in the human genome. The homogeneity of mutations in achondroplasia is unprecedented for an autosomal dominant disorder and may explain the relative lack of heterogeneity in the achondroplasia phenotype. 52 refs., 1 fig., 1 tab.
- OSTI ID:
- 70397
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 2 Vol. 56; ISSN 0002-9297; ISSN AJHGAG
- Country of Publication:
- United States
- Language:
- English
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