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Identification of four novel connexin 26 mutations in non-syndromic deaf patients: genotype–phenotype analysis in moderate cases

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Abstract

This paper presents a mutation as well as a genotype–phenotype analysis of the GJB2 and GJB6 genes in 476 samples from non-syndromic unrelated Argentinean deaf patients (104 familial and 372 sporadic cases). Most of them were of prelingual onset (82 %) and 27 % were cochlear implanted. Variation of sequences was detected in 171 of the 474 patients (36 %). Overall, 43 different sequence variations were identified in GJB2 and GJB6. Four of them are reported for the first time in GJB2: c.233dupG, p.Ala78Ser, p.Val190Asp and p.Cys211Tyr. Mutations in GJB6 were detected in 3 % of patients [nine del(GJB6-D13S1830) and three del(GJB6-D13S1854)]. Of the 43 different variations identified in GJB2, 6 were polymorphisms and of the others, 10 (27 %) were truncating and 27 (73 %) were nontruncating. Patients with two truncating mutations had significantly worse hearing impairment than all other groups. Moderate phenotypes were observed in a group of patients carrying biallelic mutations (23 %). This work shows the high prevalence of GJB2 mutations in the Argentinean population and presents an analysis of moderate phenotypes in our cohort.

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Acknowledgments

We would like to thank all families that participated in this study. This study was supported by an International Research Scholar grant from the Howard Hughes Medical Institute and the Tinnitus Research Initiative to Ana Belen Elgoyhen and by ANPCyT, Argentina, to Viviana Dalamon. María Florencia Wernert is a CONICET fellow.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Dr. Héctor N. Torres (INGEBI) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina

    Viviana Dalamón, M. Florencia Wernert & Ana Belén Elgoyhen

  2. Servicio de Genética, Hospital de Clínicas “José de San Martín”, C1120AAR, Ciudad Autónoma de Buenos Aires, Argentina

    Vanesa Lotersztein

  3. Departamento de Química Biológica e Instituto de Química y Fisicoquímica Biológicas, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (UBA-CONICET), Ciudad Autónoma de Buenos Aires, Argentina

    Patricio O. Craig

  4. Centro Piloto de Detección de Errores Metabólicos (CEPIDEM), Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, UNC, Córdoba, Argentina

    Raúl Reynoso Diamante, María E. Barteik & Carlos Curet

  5. Centro Otoaudiológico de Alta Tecnología (COAT), Facultad de Ciencias Médicas, UNC, Córdoba, Argentina

    Raúl Reynoso Diamante, María E. Barteik & Carlos Curet

  6. Servicio de Otorrinolaringología Infantil, Hospital de Clínicas “José de San Martín”, Ciudad Autónoma de Buenos Aires, Argentina

    Bibiana Paoli & Enrique Mansilla

  7. Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires (UBA), Ciudad Autónoma de Buenos Aires, Argentina

    Ana Belén Elgoyhen

Authors
  1. Viviana Dalamón
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  2. M. Florencia Wernert
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  3. Vanesa Lotersztein
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  4. Patricio O. Craig
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  5. Raúl Reynoso Diamante
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  6. María E. Barteik
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  7. Carlos Curet
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  8. Bibiana Paoli
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  9. Enrique Mansilla
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  10. Ana Belén Elgoyhen
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Corresponding author

Correspondence to Viviana Dalamón.

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Dalamón, V., Florencia Wernert, M., Lotersztein, V. et al. Identification of four novel connexin 26 mutations in non-syndromic deaf patients: genotype–phenotype analysis in moderate cases. Mol Biol Rep 40, 6945–6955 (2013). https://doi.org/10.1007/s11033-013-2814-x

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  • DOI: https://doi.org/10.1007/s11033-013-2814-x

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