Skip to main content
SpringerLink
Log in

Changes in the connexin 26 gene (GJB2) in Russian patients with hearing loss: Results of long-term molecular diagnostics of hereditary nonsyndromic hearing loss

  • Human Genetics
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

Molecular testing for mutations in the connexin 26 gene (GJB2) is a routine diagnostic analysis for subjects with hereditary hearing loss worldwide. However, till now there is no assessment of the diagnostic significance of this analysis for Russian patients, and there are difficulties in interpretation of the results of DNA diagnostics. In the present study, a sample of 705 patients with nonsyndromic autosomal recessive hearing loss from different regions of Russian Federation was investigated. A portion of DFNB1 hearing loss caused by mutations in the GJB2 gene among the sample was 46%. The frequency of DFNB1 hearing loss was 1:1000, that is, the frequency of isolated autosomal recessive hearing loss 1:500 in the population. It was found that each sixteenth individual in Russia is a heterozygous carrier of the mutation in the GJB2 gene. Totally, 20 pathological GJB2 alleles were detected; among them, a c.35delG mutation with the allelic frequency 81% prevails. Six most frequent mutations (c.35delG, c.313_326del14, c.23+1G>A (IVS1+1G>A), c.235delC, c.167delT, and p.Glu120del), which account for 95% of pathological GJB2 alleles, were detected. Mutations previously not described in the GJB2 gene (c.129delG, p.Gly200Arg, and c[Arg127His, Gly160Ser]) were found. An optimal algorithm of molecular testing of Russian patients which detects up to 100% of mutations in the GJB2 gene was suggested. Data concerning a clinical significance of p.Met34Thr and p.Val37Ile mutations are confirmed in the study. Eight polymorphic substitutions in the GJB2 gene which do not have clinical significance (p.Val27Ile, c.*3C>A, p.Val153Ile, p.Gly160Ser, c.Arg127His, p.Glu114Gly (c.341A>G), c.-45C>A, and p.Ala149Thr) were also detected.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Morton, C.C. and Nance, W.E., Newborn Hearing Screening—a Silent Revolution, New England J. Med., 2006, vol. 354, no. 20, pp. 2151–2164.

    Article  CAS  Google Scholar 

  2. Bauer, P.W., Geers, A.E., Brenner, C., et al., The Effect of GJB2 Allele Variants on Performance after Cochlear Implantation, Laryngoscope, 2003, vol. 113, no. 12, pp. 2135–2140.

    Article  PubMed  CAS  Google Scholar 

  3. Smith, R.J., Bale, J.F., and White, K.R., Sensorineural Hearing Loss in Children, Lancet, 2005, vol. 365, no. 9462, pp. 879–890.

    Article  PubMed  Google Scholar 

  4. Yoshinaga-Itano, C., Early Intervention after Universal Neonatal Hearing Screening: Impact on Outcomes, Ment. Retard Dev. Disabil. Res. Rev., 2003, vol. 9, no. 4, pp. 252–266..

    Article  PubMed  Google Scholar 

  5. Tavarkiladze, G.A., Polyakov, A.V., Markova, T.G., et al., Genetic Screening for Hearing Disorders in Newborn Infants in Combination with Audiological Screening, Vestn. Otorinolaryngol., 2010, vol. 3, no. 15, pp. 15–18.

    Google Scholar 

  6. Wang, Q.J., Zhao, Y.L., Rao, S.Q., et al., Newborn Hearing Concurrent Gene Screening Can Improve Care for Hearing Loss: A Study on 14.913 Chinese Newborns, Int. J. Pediatr. Otorhinolaryngol., 2011, vol. 75, no. 4, pp. 535–542.

    Article  PubMed  Google Scholar 

  7. Van Camp, G., Willems, P.J., and Smith, R.J., Nonsyndromic Hearing Impairment: Unparalleled Heterogeneity, Am. J. Hum. Genet., 1997, vol. 60, no. 4, pp. 758–764.

    PubMed  Google Scholar 

  8. Morton, N.E., Genetic Epidemiology of Hearing Impairment, Ann. N.Y. Acad. Sci., 1991, vol. 630, pp. 16–31.

    Article  PubMed  CAS  Google Scholar 

  9. Tekin, M., Arnos, K.S., and Pandya, A., Advances in Hereditary hearing loss, Lancet, 2001, vol. 358, no. 9287, pp. 1082–1090.

    Article  PubMed  CAS  Google Scholar 

  10. Zinchenko, S.P., Kirillov, A.G., Abrukova, A.G., et al., Genetic and Epidemiological Study of Hereditary (Isolated and Syndromal) Hearing Impairment in the Chuvash Republic, Med. Genet., 2007, vol. 6, no. 5, pp. 19–29.

    Google Scholar 

  11. Shokarev, R.A., Amelina, S.S., Kriventsova, N.V., et al., Genetic, Epidemiological and Molecular Study of Hereditary Hearing Loss in Rostov Oblast, Med. Genet., 2005, vol. 4, no. 12, pp. 556–565.

    Google Scholar 

  12. Hilgert, N., Smith, R.J., and Van Camp, G., Forty-Six Genes Causing Nonsyndromic Hearing Impairment: Which Ones Should Be Analyzed in DNA Diagnostics?, Mutat. Res., 2009, vol. 681, nos. 2–3, pp. 189–196.

    PubMed  CAS  Google Scholar 

  13. Van Camp, G., and Smith, R., The Hereditary Hearing Loss Homepage, hereditaryhearingloss.org.

  14. Bruzzone, R., White, T.W., and Goodenough, D.A., The Cellular Internet: On-Line with Connexins, BioEssays, 1996, vol. 18, no. 9, pp. 709–718.

    Article  PubMed  CAS  Google Scholar 

  15. Harris, A.L. and Bevans, C.G., Exploring Hemichannel Permeability in vitro, Methods Mol. Biol., 2001, vol. 154, pp. 357–377.

    PubMed  CAS  Google Scholar 

  16. Stauffer, K.A., The Gap Junction Proteins Beta 1-Connexin (Connexin-32) and Beta 2-Connexin (Connexin-26) Can Form Heteromeric Hemichannels, J. Biol. Chem., 1995, vol. 270, no. 12, pp. 6768–6772.

    PubMed  CAS  Google Scholar 

  17. Beltramello, M., Piazza, V., Bukauskas, F.F., et al., Impaired Permeability to Ins(1.4,5)P3 in a Mutant Connexin Underlies Recessive Hereditary hearing loss, Nat. Cell Biol., 2005, vol. 7, no. 1, pp. 63–69.

    Article  PubMed  CAS  Google Scholar 

  18. Choudhry, R., Pitts, J.D., and Hodgins, M.B., Changing Patterns of Gap Junctional Intercellular Communication and Connexin Distribution in Mouse Epidermis and Hair Follicles during Embryonic Development, Dev. Dyn., 1997, vol. 210, no. 4, pp. 417–430.

    Article  PubMed  CAS  Google Scholar 

  19. Kikuchi, T., Kimura, R.S., Paul, D.L., et al., Gap Junctions in the Rat Cochlea: Immunohistochemical and Ultrastructural Analysis, Anat. Embryol. (Berlin), 1995, vol. 191, no. 2, pp. 101–118.

    CAS  Google Scholar 

  20. Ballana, E., Ventayol, M., Rabionet, R., et al., Connexins and hearing loss Homepage, http://www.crg.es/hearingloss.

  21. Feldmann, D., Denoyelle, F., Blons, H., et al., The GJB2 Mutation R75Q Can Cause Nonsyndromic Hearing Loss DFNA3 or Hereditary Palmoplantar Keratoderma with hearing loss, Am. J. Med. Genet., 2005, vol. 137, no. 2, pp. 225–227.

    Article  PubMed  Google Scholar 

  22. Primignani, P., Trotta, L., Castorina, P., et al., A New de novo Missense Mutation in Connexin 26 in a Sporadic Case of Nonsyndromic hearing loss, Laryngoscope, 2007, vol. 117, no. 5, pp. 821–824.

    Article  PubMed  Google Scholar 

  23. Matos, T.D., Caria, H., Simoes-Teixeira, H., et al., A Novel M163L Mutation in Connexin 26 Causing Cell Death and Associated with Autosomal Dominant Hearing Loss, Hear Res., 2008, vol. 240, nos. 1–2, pp. 87–92.

    Article  PubMed  CAS  Google Scholar 

  24. Piazza, V., Beltramello, M., Menniti, M., et al., Functional Analysis of R75Q Mutation in the Gene Coding for Connexin 26 Identified in a Family with Nonsyndromic Hearing Loss, Clin. Genet., 2005, vol. 68, no. 2, pp. 161–166.

    Article  PubMed  CAS  Google Scholar 

  25. Lee, J.R. and White, T.W., Connexin-26 Mutations in hearing loss and Skin Disease, Expert. Rev. Mol. Med., 2009, vol. 11, p. e35.

    Article  PubMed  Google Scholar 

  26. del Castillo, F.J., Rodriguez-Ballesteros, M., Alvarez, A., et al., A Novel Deletion Involving the Connexin-30 Gene, del(GJB6-D13S1854), Found in Trans with Mutations in the GJB2 Gene (Connexin-26) in Subjects with DFNB1 Non-Syndromic Hearing Impairment, J. Med. Genet., 2005, vol. 42, no. 7, pp. 588–594.

    Article  PubMed  Google Scholar 

  27. Snoeckx, R.L., Huygen, P.L., Feldmann, D., et al., GJB2 Mutations and Degree of Hearing Loss: A Multicenter Study, Am. J. Hum. Genet., 2005, vol. 77, no. 6, pp. 945–957.

    Article  PubMed  CAS  Google Scholar 

  28. Common, J.E., Bitner-Glindzicz, M., O’Toole, E.A., et al., Specific Loss of Connexin 26 Expression in Ductal Sweat Gland Epithelium Associated with the Deletion Mutation del(GJB6-D13S1830), Clin. Exp. Dermatol., 2005, vol. 30, no. 6, pp. 688–693.

    Article  PubMed  CAS  Google Scholar 

  29. Wilch, E., Zhu, M., Burkhart, K.B., et al., Expression of GJB2 and GJB6 Is Reduced in a Novel DFNB1 Allele, Am. J. Hum. Genet., 2006, vol. 79, no. 1, pp. 174–179.

    Article  PubMed  CAS  Google Scholar 

  30. Grifa, A., Wagner, C.A., D’Ambrosio, L., et al., Mutations in GJB6 Cause Nonsyndromic Autosomal Dominant hearing loss at DFNA3 Locus, Nat. Genet., 1999, vol. 23, no. 1, pp. 16–18.

    Article  PubMed  CAS  Google Scholar 

  31. Smith, F.J., Morley, S.M., and McLean, W.H., A Novel Connexin 30 Mutation in Clouston Syndrome, J. Invest. Dermatol., 2002, vol. 118, no. 3, pp. 530–532.

    Article  PubMed  CAS  Google Scholar 

  32. Posukh, O., Pallares-Ruiz, N., Tadinova, V., et al., First Molecular Screening of hearing loss in the Altai Republic Population, BMC Med. Genet., 2005, vol. 6, p. 12.

    Article  PubMed  Google Scholar 

  33. Barashkov, N.A., Dzhemileva, L.U., Fedorova, S.A., et al., Connexin 26 Gene (GJB2) Mutations in Patients with Hereditary Non-Syndromic Sensorineural Loss of Hearing in the Republic of Sakha (Yakutia), Vestn. Otolaringol., 2008, no. 5, pp. 23–28.

  34. Osetrova, A.A., Sharonova, E.I., and Rossinskaya, T.G., Study of Genetic Basis of Hereditary and Early Children Hearing Loss in Specialized Schools for Children with Hearing Impairment in Kirov Oblast, Med. Genet., 2010, vol. 9, no. 9, pp. 30–40.

    Google Scholar 

  35. Nekrasova, N.Yu., Shagina, I.A., Petrin, A.N., and Polyakov, A.V., A Frequency of Connexin 26 Gene 35delG Mutation in Children with Sensorineural Hearing Loss, Med. Genet., 2002, vol. 1, no. 6, pp. 290–294.

    Google Scholar 

  36. Markova, T.G., Nekrasova, N.V., Shagina, I.A., and Polyakov, A.V., Genetic Screening among Children with Hereditary and Early Hearing Loss, Vestn. Otorinolaringol., 2006, no. 4, pp. 9–14.

  37. Hamelmann, C., Amedofu, G.K., Albrecht, K., et al., Pattern of Connexin 26 (GJB2) Mutations Causing Sensorineural Hearing Impairment in Ghana, Hum. Mutat., 2001, vol. 18, no. 1, pp. 84–85.

    Article  PubMed  CAS  Google Scholar 

  38. Lingala, H.B. and Penagaluru, P.R., Role of Connexin 26 (GJB2) and Mitochondrial Small Ribosomal RNA (mt 12S rRNA) Genes in Sporadic and Aminoglycoside-Induced Non-Syndromic Hearing Impairment, Indian J. Med. Res., 2009, vol. 130, no. 4, pp. 369–378.

    PubMed  CAS  Google Scholar 

  39. Zhuravskii, S.G., Ivanov, S.A., Taraskina, A.E., et al., Distribution of “Deaf” 35delG Mutation of GJB2 Gene among Healthy Population of the Northwestern Region of Russia, Med. Akad. Zh., 2009, vol. 9, no. 2, pp. 41–45.

    Google Scholar 

  40. Dzhemileva, L.U., Barashkov, N.A., Posukh, O.L., et al., Analysis of Heterozygous Carriage of 35delG, 235delC, and 167delT Mutations in GJB2 Gene among Populations of Eurasia, Med. Genet., 2009, vol. 8, no. 8, pp. 20–28.

    CAS  Google Scholar 

  41. Barashkov, N.A., Dzhemileva, L.U., Fedorova, S.A., et al., Contribution of 35delG, 235delC, and 167delT Mutations in Connexin 26 Gene, GJB2, into Appearance of Hereditary Non-Syndromic Hearing Loss in the Republic of Sakha (Yakutia), Med. Genet., 2007, vol. 6, no. 9, pp. 26–30.

    Google Scholar 

  42. Anichkina, A., Kulenich, T., Zinchenko, S., et al., On the Origin and Frequency of the 35delG Allele in GJB2-Linked hearing loss in Europe, Eur. J. Hum. Genet., 2001, vol. 9, no. 2, p. 151.

  43. Gasparini, P., Rabionet, R., Barbujani, G., et al., High Carrier Frequency of the 35delG hearing loss Mutation in European Populations, Eur. J. Hum. Genet., 2000, vol. 8, pp. 19–23.

    Article  PubMed  CAS  Google Scholar 

  44. Smith, R.J. and Van Camp, G., Nonsyndromic Hearing Loss and hearing loss, DFNB1, 2008, http://www.ncbi. nlm.nih.gov/books.

  45. Barashkov, N.A., Dzhemileva, L.U., Fedorova, S.A., et al., Mutation of q.-3179(IVS1+1GA) Splicing Site of the GJB2 Gene—the Main Cause of Hereditary Non-Syndromic Autosome-Recessive hearing loss among Yakuts, Med. Genet., 2010, vol. 9, no. 7, pp. 22–32.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Center for Medical Genetics, Russian Academy of Medical Sciences, Moscow, 115478, Russia

    E. A. Bliznetz, V. A. Galkina, G. N. Matyushchenko & A. V. Polyakov

  2. National Research Centre for Audiology and Hearing Rehabilitation, Federal Medical and Biological Agency, Moscow, 117513, Russia

    T. G. Markova

  3. Children’s Audiology Center, Moscow, 119311, Russia

    A. G. Kisina

Authors
  1. E. A. Bliznetz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. A. Galkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. N. Matyushchenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. G. Kisina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. G. Markova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. V. Polyakov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. A. Bliznetz.

Additional information

Original Russian Text © E.A. Bliznetz, V.A. Galkina, G.N. Matyushchenko, A.G. Kisina, T.G. Markova, A.V. Polyakov, 2012, published in Genetika, 2012, Vol. 48, No. 1, pp. 112–124.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bliznetz, E.A., Galkina, V.A., Matyushchenko, G.N. et al. Changes in the connexin 26 gene (GJB2) in Russian patients with hearing loss: Results of long-term molecular diagnostics of hereditary nonsyndromic hearing loss. Russ J Genet 48, 101–112 (2012). https://doi.org/10.1134/S1022795412010036

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795412010036

Keywords

Search

Navigation