BACKGROUND: In the present study we aimed: 1) To establish the prevalence and clinical impact of DFNB49 mutations in deaf Roma from 2 Central European countries (Slovakia and Hungary), and 2) to analyze a possible common origin of the c.1331+2T>C mutation among Roma and Pakistani mutation carriers identified in the present and previous studies. METHODS: We sequenced 6 exons of the MARVELD2 gene in a group of 143 unrelated hearing impaired Slovak Roma patients. Simultaneously, we used RFLP to detect the c.1331+2T>C mutation in 85 Hungarian deaf Roma patients, control groups of 702 normal hearing Romanies from both countries and 375 hearing impaired Slovak Caucasians. We analyzed the haplotype using 21 SNPs spanning a 5.34Mb around the mutation c.1331+2T>C. RESULTS: One pathogenic mutation (c.1331+2T>C) was identified in 12 homozygous hearing impaired Roma patients. Allele frequency of this mutation was higher in Hungarian (10%) than in Slovak (3.85%) Roma patients. The identified common haplotype in Roma patients was defined by 18 SNP markers (3.89 Mb). Fourteen common SNPs were also shared among Pakistani and Roma homozygotes. Biallelic mutation carriers suffered from prelingual bilateral moderate to profound sensorineural hearing loss. CONCLUSIONS: We demonstrate different frequencies of the c.1331+2T>C mutation in hearing impaired Romanies from 3 Central European countries. In addition, our results provide support for the hypothesis of a possible common ancestor of the Slovak, Hungarian and Czech Roma as well as Pakistani deaf patients. Testing for the c.1331+2T>C mutation may be recommended in GJB2 negative Roma cases with early-onset sensorineural hearing loss.

Department of Medical Genetics University of Pécs Clinical Centre Pécs Hungary

Department of Medical Genetics University of Pécs Clinical Centre Pécs Hungary; Szentagothai Research Centre University of Pécs Pécs Hungary

Department of Molecular Biology Faculty of Natural Sciences Comenius University Bratislava Slovakia

Department of Molecular Biology Faculty of Natural Sciences Comenius University Bratislava Slovakia; Institute of Molecular Physiology and Genetics Slovak Academy of Sciences Bratislava Slovakia

Department of Otorhinolaryngology Head and Neck Surgery Faculty Hospital of J A Reiman Prešov Slovakia

Department of Otorhinolaryngology Head and Neck Surgery Faculty of Medicine and University Hospital Comenius University Bratislava Slovakia

Department of Otorhinolaryngology Head and Neck Surgery School of Medicine University of Maryland Baltimore Maryland United States of America

DNA Laboratory Department of Paediatric Neurology Charles University 2nd Medical School and University Hospital Motol Prague Czech Republic

Laboratory of Diabetes and Metabolic Disorders and DIABGENE Institute of Experimental Endocrinology Slovak Academy of Sciences Bratislava Slovakia

Laboratory of Diabetes and Metabolic Disorders and DIABGENE Institute of Experimental Endocrinology Slovak Academy of Sciences Bratislava Slovakia; Center for Molecular Medicine Slovak Academy of Sciences Bratislava Slovakia

Laboratory of Diabetes and Metabolic Disorders and DIABGENE Institute of Experimental Endocrinology Slovak Academy of Sciences Bratislava Slovakia; Department of Otorhinolaryngology Head and Neck Surgery Faculty of Medicine and University Hospital Comenius University Bratislava Slovakia

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