title: Homozygous mutations in fibroblast growth factor 3 are associated with a new form of syndromic deafness characterized by inner ear agenesis, microtia, and microdontia.
abstract: We identified nine individuals from three unrelated Turkish families with a unique autosomal recessive syndrome characterized by type I microtia, microdontia, and profound congenital deafness associated with a complete absence of inner ear structures (Michel aplasia). We later demonstrated three different homozygous mutations (p.S156P, p.R104X, and p.V206SfsX117) in the fibroblast growth factor 3 (FGF3) gene in affected members of these families, cosegregating with the autosomal recessive transmission as a completely penetrant phenotype. These findings demonstrate the involvement of FGF3 mutations in a human malformation syndrome for the first time and contribute to our understanding of the role this gene plays in embryonic development. Of particular interest is that the development of the inner ear is completely disturbed at a very early stage--or the otic vesicle is not induced at all--in all of the affected individuals who carried two mutant FGF3 alleles.
authors.affiliation: Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey. mtekin@medicine.ankara.edu.tr
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
authors.forename: Burcu Oztürk
authors.initials: BO
authors.lastname: Hişmi
authors.forename: Suat
authors.initials: S
authors.lastname: Fitoz
authors.forename: Hilal
authors.initials: H
authors.lastname: Ozdağ
authors.forename: Filiz Başak
authors.initials: FB
authors.lastname: Cengiz
authors.forename: Asli
authors.initials: A
authors.lastname: Sirmaci
authors.forename: Idil
authors.initials: I
authors.lastname: Aslan
authors.forename: Bora
authors.initials: B
authors.lastname: Inceoğlu
authors.forename: E Berrin
authors.initials: EB
authors.lastname: Yüksel-Konuk
authors.forename: Seda Taşir
authors.initials: ST
authors.lastname: Yilmaz
authors.forename: Oztan
authors.initials: O
authors.lastname: Yasun
authors.forename: Nejat
authors.initials: N
authors.lastname: Akar
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D003638:Deafness / Q000151:congenital / Q000235:genetics*; D007758:Ear, Inner / Q000002:abnormalities*; D005260:Female; D051518:Fibroblast Growth Factor 3 / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014071:Tooth Abnormalities / Q000235:genetics*
chemical_list: C496444:FGF3 protein, human; D051518:Fibroblast Growth Factor 3