title: Syndromic congenital sensorineural deafness, microtia and microdontia resulting from a novel homoallelic mutation in fibroblast growth factor 3 (FGF3).
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.
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
authors.forename: Osama
authors.initials: O
authors.lastname: Alsmadi
authors.forename: Brian F
authors.initials: BF
authors.lastname: Meyer
authors.forename: Fowzan
authors.initials: F
authors.lastname: Alkuraya
authors.forename: Salma
authors.initials: S
authors.lastname: Wakil
authors.forename: Fadi
authors.initials: F
authors.lastname: Alkayal
authors.forename: Haya
authors.initials: H
authors.lastname: Al-Saud
authors.forename: Khushnooda
authors.initials: K
authors.lastname: Ramzan
authors.forename: MoeenAldeen
authors.initials: M
authors.lastname: Al-Sayed
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003241:Consanguinity; D003638:Deafness / Q000235:genetics*; D004431:Ear, External / Q000002:abnormalities*; D007758:Ear, Inner / Q000002:abnormalities*; D005260:Female; D051518:Fibroblast Growth Factor 3 / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D013577:Syndrome; D014071:Tooth Abnormalities / Q000235:genetics*; D055815:Young Adult
chemical_list: C496444:FGF3 protein, human; D051518:Fibroblast Growth Factor 3