title: MARVELD2 (DFNB49) mutations in the hearing impaired Central European Roma population--prevalence, clinical impact and the common origin.
abstract: 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.
authors.affiliation: Laboratory of Diabetes and Metabolic Disorders & DIABGENE, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Ivica
authors.initials: I
authors.lastname: Mašindová
authors.affiliation: Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia; Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Šoltýsová
authors.affiliation: Laboratory of Diabetes and Metabolic Disorders & 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.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Varga
authors.affiliation: Department of Medical Genetics, University of Pécs, Clinical Centre, Pécs, Hungary.
authors.forename: Petra
authors.initials: P
authors.lastname: Mátyás
authors.affiliation: Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
authors.forename: Andrej
authors.initials: A
authors.lastname: Ficek
authors.affiliation: Laboratory of Diabetes and Metabolic Disorders & DIABGENE, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia; Center for Molecular Medicine, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Miloslava
authors.initials: M
authors.lastname: Hučková
authors.affiliation: Laboratory of Diabetes and Metabolic Disorders & DIABGENE, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Martina
authors.initials: M
authors.lastname: Sůrová
authors.affiliation: DNA Laboratory, Department of Paediatric Neurology, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Šafka-Brožková
authors.affiliation: Department of Otorhinolaryngology Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: Saima
authors.initials: S
authors.lastname: Anwar
authors.affiliation: Department of Medical Genetics, University of Pécs, Clinical Centre, Pécs, Hungary; Szentagothai Research Centre, University of Pécs, Pécs, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Bene
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Faculty Hospital of J. A. Reiman, Prešov, Slovakia.
authors.forename: Slavomír
authors.initials: S
authors.lastname: Straka
authors.affiliation: Department of Medical Genetics, University of Pécs, Clinical Centre, Pécs, Hungary.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Janicsek
authors.affiliation: Department of Otorhinolaryngology Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: Zubair M
authors.initials: ZM
authors.lastname: Ahmed
authors.affiliation: DNA Laboratory, Department of Paediatric Neurology, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Seeman
authors.affiliation: Department of Medical Genetics, University of Pécs, Clinical Centre, Pécs, Hungary; Szentagothai Research Centre, University of Pécs, Pécs, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University, Bratislava, Slovakia.
authors.forename: Milan
authors.initials: M
authors.lastname: Profant
authors.affiliation: Laboratory of Diabetes and Metabolic Disorders & DIABGENE, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Iwar
authors.initials: I
authors.lastname: Klimeš
authors.affiliation: Department of Otorhinolaryngology Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: Saima
authors.initials: S
authors.lastname: Riazuddin
authors.affiliation: Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia; Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Ľudevít
authors.initials: Ľ
authors.lastname: Kádasi
authors.affiliation: Laboratory of Diabetes and Metabolic Disorders & DIABGENE, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia; Center for Molecular Medicine, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gašperíková
mesh_terms: D017668:Age of Onset; D000483:Alleles; D000072259:Connexin 26; D017630:Connexins; D018153:Czech Republic / Q000208:ethnology; D005091:Exons / Q000235:genetics; D018703:Founder Effect; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D034381:Hearing Loss / Q000151:congenital / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D006814:Hungary / Q000208:ethnology; D007223:Infant; D062794:MARVEL Domain Containing 2 Protein / Q000235:genetics*; D009154:Mutation; D010154:Pakistan / Q000208:ethnology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D006178:Romani People / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D018154:Slovakia / Q000208:ethnology
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D062794:MARVEL Domain Containing 2 Protein; C516798:MARVELD2 protein, human; D000072259:Connexin 26