Spectrum and frequency of SLC26A4 mutations among Czech patients with early hearing loss with and without Enlarged Vestibular Aqueduct (EVA).
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.
Pourová
Radka
R
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
Janousek
Petr
P
Jurovcík
Michal
M
Dvoráková
Marcela
M
Malíková
Marcela
M
Rasková
Dagmar
D
Bendová
Olga
O
Leonardi
Emanuela
E
Murgia
Alessandra
A
Kabelka
Zdenek
Z
Astl
Jaromír
J
Seeman
Pavel
P
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
D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26