1. ¹Arabian Diagnostic Laboratories, Department of Genetics, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
2. ²Department of Medical Genetics, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia

Correspondence: Dr MA Al-Sayed, Department of Medical Genetics, King Faisal Specialist Hospital & Research Center, P.O. Box 3354, MBC 75, Riyadh 11211, Saudi Arabia. Tel: +96 612 055 162; Fax: +96 612 055 171; E-mail: moeen@kfshrc.edu.sa

Received 5 January 2008; Revised 26 June 2008; Accepted 2 July 2008; Published online 13 August 2008.

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 '-trefoil fold' characteristic of the secondary structure of FGF family proteins and substitution of these residues is likely to disrupt structure and consequently function.