Abstract
We identified a homozygous missense mutation (c.196G -> T) in fibroblast growth factor 3 (FGF3) in 21 affected individuals from a large extended consanguineous Saudi family, phenotypically characterized by autosomal recessive syndromic congenital sensorineural deafness, microtia and microdontia. All affected family members are descendents of a common ancestor who had lived six generations ago in a geographically isolated small village. This is the second report of FGF3 involvement in syndromic deafness in humans, and independently confirms the gene's positive role in inner ear development. The c. 196G -> T mutation results in substitution of glycine by cysteine at amino acid 66 (p.G66C). This residue is conserved in several species and across 18 FGF family members. Conserved glycine/proline residues are central to the 'beta-trefoil fold' characteristic of the secondary structure of FGF family proteins and substitution of these residues is likely to disrupt structure and consequently function.