title: Specificity of SLC26A4 mutations in the pathogenesis of inner ear malformations.
abstract: The traditional hypothesis concerning the pathogenesis of inner ear malformations holds that various types of malformations represent different stages of developmental arrest during embryogenesis. In order to verify this hypothesis, we surveyed mutations in the SLC26A4(PDS) gene, which were documented to cause enlarged vestibular aqueduct (EVA) and Mondini's dysplasia (incomplete partition of the cochlea), in 35 families with various types of inner ear malformations. In 25 families, the probands showed EVA or Mondini's dysplasia as the main temporal bone abnormalities, whereas the probands in the remaining 10 families revealed other types of malformations. In total, 7 mutated SLC26A4 alleles, including 6 missense mutations (A372V, A387V, T410M, S448L, T721M, and H723R) and 1 splice site mutation (IVS7-2A-->G), were detected. All mutated alleles segregated the malformations of EVA and Mondini's dysplasia, whereas no mutated alleles were found in the 10 probands with other types of malformations. SLC26A4 mutations were found in 22 of the 25 probands with EVA or Mondini's dysplasia, indicating that these might be specific to the development of Mondini's dysplasia and EVA. It is inferred that the pathogenetic mechanisms of the various malformations essentially differ, although their radiological findings appear to follow a continuum of morphological changes.
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Chen-Chi
authors.initials: CC
authors.lastname: Wu
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Chuan-Jen
authors.initials: CJ
authors.lastname: Hsu
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003638:Deafness / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D007758:Ear, Inner / Q000002:abnormalities*; D005192:Family Health; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000002:abnormalities*
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters