title: Spectrum and frequency of SLC26A4 mutations among Czech patients with early hearing loss with and without Enlarged Vestibular Aqueduct (EVA).
abstract: Mutations in SLC26A4 cause Pendred syndrome (PS) - hearing loss with goitre - or DFNB4 - non-syndromic hearing loss (NSHL) with inner ear abnormalities such as Enlarged Vestibular Aqueduct (EVA) or Mondini Dysplasia (MD). We tested 303 unrelated Czech patients with early hearing loss (298 with NSHL and 5 with PS), all GJB2-negative, for SLC26A4 mutations and evaluated their clinical and radiological phenotype. Among 115 available HRCT/MRI scans we detected three MD (2.6%), three Mondini-like affections (2.6%), 16 EVA (13 bilateral - 19.2% and 15.6% respectively) and 61 EVA/MD-negative scans (73.4%). We found mutation(s) in 26 patients (8.6%) and biallelic mutations in eight patients (2.7%) out of 303 tested. In 18 of 26 (69%) patients, no second mutation could be detected even using MLPA. The spectrum of SLC26A4 mutations in Czech patients is broad without any prevalent mutation. We detected 21 different mutations (four novel). The most frequent mutations were p.Val138Phe and p.Leu445Trp (18% and 8.9% of pathogenic alleles respectively). Among 13 patients with bilateral EVA, six patients (50%) carry biallelic mutations. In EVA -negative patients no biallelic mutations were found but 4.9% had monoallelic mutations. SLC26A4 mutations are present mostly in patients with EVA/MD and/or progressive HL and those with affected siblings.
authors.affiliation: Department of Paediatric Neurology, DNA Laboratory, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. radka.pourova@post.cz
authors.forename: Radka
authors.initials: R
authors.lastname: Pourová
authors.forename: Petr
authors.initials: P
authors.lastname: Janousek
authors.forename: Michal
authors.initials: M
authors.lastname: Jurovcík
authors.forename: Marcela
authors.initials: M
authors.lastname: Dvoráková
authors.forename: Marcela
authors.initials: M
authors.lastname: Malíková
authors.forename: Dagmar
authors.initials: D
authors.lastname: Rasková
authors.forename: Olga
authors.initials: O
authors.lastname: Bendová
authors.forename: Emanuela
authors.initials: E
authors.lastname: Leonardi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Murgia
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Kabelka
authors.forename: Jaromír
authors.initials: J
authors.lastname: Astl
authors.forename: Pavel
authors.initials: P
authors.lastname: Seeman
mesh_terms: D000072259:Connexin 26; D017630:Connexins; D018153:Czech Republic / Q000453:epidemiology; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D000076988:Sulfate Transporters; D013577:Syndrome; D014723:Vestibular Aqueduct / Q000473:pathology
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26