title: Mutations of the Pendred syndrome gene (PDS) in patients with large vestibular aqueduct.
abstract: A recent report demonstrated the presence of a mutation in the Pendred syndrome gene (PDS) of patients with large vestibular aqueducts but without goitre. We studied PDS mutations in members of four Japanese families, among which five affected members showed bilateral enlarged vestibular aqueducts. All affected members exhibited moderate to severe bilateral fluctuating sensorineural hearing loss and the absence of goitre. Three members also suffered from recurrent episodic vertiginous spells. Analysis of PDS mutation revealed two single base changes (mis-sense mutations) in exons 19 and 10. The first was an A-->G transition at nucleotide position 2168, resulting in a predicted His-->Arg substitution at position 723 (H723R), whereas the second was a C-->T transition at nucleotide position 1229, resulting in a predicted Thr-->Met substitution at position 410 (T410M). Both mutations are situated in the extracellular domain close to the C terminal. It thus appears that PDS mutations can lead not only to classic Pendred syndrome, but also to large vestibular aqueduct syndrome.
authors.affiliation: Department of Otolaryngology, School of Medicine, Tokyo Medical and Dental University, Japan. kitamura.oto@med.tmd.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Kuroishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Tamagawa
authors.forename: K
authors.initials: K
authors.lastname: Ishikawa
authors.forename: K
authors.initials: K
authors.lastname: Ichimura
authors.forename: H
authors.initials: H
authors.lastname: Hagiwara
mesh_terms: D000293:Adolescent; D000328:Adult; D001301:Audiometry, Pure-Tone; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006042:Goiter / Q000175:diagnosis / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins; D000076988:Sulfate Transporters; D013577:Syndrome; D014057:Tomography, X-Ray Computed; D014723:Vestibular Aqueduct / Q000002:abnormalities* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters