Genotyping of the C742T mutation of the FGFR3 gene causing type 1 thanatophoric dysplasia by high-resolution melting analysis

Abstract

Type 1 thanatophoric dysplasia (TD) is typically a lethal dwarfism. It is not always possible to distinguish fetuses with TD from other skeletal dysplasia in utero by ultrasonography. A definite diagnosis should be established by molecular genetic analysis to find out the abnormal mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene. Among the known mutations of this gene, the C742T (R248C) mutation is the most common one associated with type 1 TD. Exon 7 of the FGFR3 gene was analyzed in 10 prenatal samples with type 1 TD, as well as in 30 control individuals for the presence of the c.742 C > T variant using melting curve analysis with a high-resolution melting instrument. The high-resolution melting curve analysis successfully genotyped this mutation in all 10 samples with type 1 TD without the need of further assays. The technique had a sensitivity and specificity of 100%. This study suggest that high-resolution melting analysis is a simple, rapid, and sensitive one tube assay for genotyping the FGFR3 gene.

Keywords:

• FGFR3 gene
• type 1 thanatophoric dysplasia
• high-resolution melting analysis

Acknowledgements

This study was supported in part by the Science and Technology Committee of Guangdong Province (2008B080702011) and by the Science and Technology Bureau of Guangzhou City (2009Z1-E131).