Abstract
Sensorineural hearing loss is the most frequent sensory deficit of childhood and is of genetic origin in up to 75% of cases. It has been shown that mutations of the SLC26A4 (PDS) gene were involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4). While the prevalence of SLC26A4 mutations in Pendred's syndrome is clearly established, it remains to be studied in large cohorts of patients with nonsyndromic deafness and detailed clinical informations. In this report, 109 patients from 100 unrelated families, aged from 1 to 32 years (median age: 10 years), with nonsyndromic deafness and enlarged vestibular aqueduct, were genotyped for SLC26A4 using DHPLC molecular screening and sequencing. In all, 91 allelic variants were observed in 100 unrelated families, of which 19 have never been reported. The prevalence of SLC26A4 mutations was 40% (40/100), with biallelic mutation in 24% (24/100), while six families were homozygous. All patients included in this series had documented deafness, associated with EVA and without any evidence of syndromic disease. Among patients with SLC26A4 biallelic mutations, deafness was more severe, fluctuated more than in patients with no mutation. In conclusion, the incidence of SLC26A4 mutations is high in patients with isolated deafness and enlarged vestibular aqueduct and could represent up to 4% of nonsyndromic hearing impairment. SLC26A4 could be the second most frequent gene implicated in nonsyndromic deafness after GJB2, in this Caucasian population.
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Acknowledgements
We are grateful to the members of the families for their cooperation in this study. This work is supported by the grant (PHRC 2002) from the Ministère de la santé, de la famille et des personnes handicapées, by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Fondation pour la Recherche Médicale and the association ‘S'entendre’. We wish to acknowledge the Direction Régionale de la Recherche Clinique (DRRC), Pr P Jaillon and Dr T Simon from the Unité de Recherche Clinique de l'Est Parisien (URCEST) for their assistance in this project.
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Albert, S., Blons, H., Jonard, L. et al. SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations. Eur J Hum Genet 14, 773–779 (2006). https://doi.org/10.1038/sj.ejhg.5201611
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DOI: https://doi.org/10.1038/sj.ejhg.5201611
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