Skip to main content
The Egyptian Journal of Otolaryngology
Download PDF

Genetic study of autosomal recessive nonsyndromic sensorineural hearing loss in Kuwaiti children

The Egyptian Journal of Otolaryngology volume 28, pages 35–43 (2012)Cite this article

En

Abstract

Background

The prevalence of congenital hearing loss was found to be one in 1000 of live births. Fifty percent of the cause is genetic and autosomal recessive nonsyndromic sensorineural hearing loss (ARNSNHL) is responsible for 80% of the genetic causes.

Study design

Descriptive cross-sectional study.

Objectives

To study the genetic causes of ARNSNHL, mainly mutation in the gene encoding connexin26 (Cx26), and to correlate the identified gene and mutation with the degree and configuration of hearing loss, the progressiveness of hearing loss, as well as its relation to language development.

Patients and methods

One hundred children, age ranging from 6 months to 18 years, presenting with congenital ARNSNHL were chosen. Behavioral observation audiometry or pure tone audiometry to identify the hearing threshold level of the children was performed. Imittancemetry, otoacoustic emissions, auditory brainstem response, and computed tomography scan study were also undertaken. In addition, genetic tests to detect Cx26 mutations using a PCR and primers, as well as sequencing using different primers were also undertaken.

Results

Out of the total of 100 cases, 15 children were shown to have positive results for Cx26; nine of these were heterozygous and six were homozygous. Twelve participants (80%) among the Cx26 cases were due to 35delG. Out of the nine children who were heterozygous, six showed positive results for D1 (35delG), whereas three children were found to have positive results for D2 (G2A at location base 71). All the six homozygous cases were shown to be positive for D1 (35delG). Thus, the results revealed that 80% of the positive genetic results cases had 35delG.

Conclusion

Eighty percent of the cause of ARNSNHL in a Kuwaiti population was the 35delG mutation and 20% was due to G2A at location base 71. Of all the cases, 57% showed a positive family history of hearing loss. The homozygous cases presented with more severe clinical pictures compared with the heterozygous cases.

References

  1. Angeli SI, Yan D, Telischi F, Balkany TJ, Ouyang XM, Du LL, et al. Etiologic diagnosis of sensorineural hearing loss in adults. Otolaryngol Head Neck Surg. 2005; 132: 890–895

    Article  Google Scholar 

  2. Shen J, Deskin RW, Quinn JFB, Ryan MW Genetic hearing loss. 2004; Available at: www.utmb.edu/otoref/grnds/…hl-2004…/genetic-hl-2004-0317.doc [Accessed March 2009]

  3. Zhao HB, Yu N. Distinct and gradient distributions of connexin26 and connexin 30 in the cochlear sensory epithelium of guinea pigs. J Comp Neurol. 2006; 499: 506–518

    Article  CAS  Google Scholar 

  4. Kemp DT. Otoacoustic emissions, travelling waves and cochlear mechanisms. Hear Res. 1986; 22: 95–104

    Article  CAS  Google Scholar 

  5. Mahdieh N, Nishimura C, Ali Madadi K, Riazalhosseini Y, Yazdan H, Arzhangi S, et al. The frequency of GJB2 mutations and the Δ (GJB6-D13S1830) deletion as a cause of autosomal recessive non-syndromic deafness in the Kurdish population. Clin Genet. 2004;65:506–508

    Article  CAS  Google Scholar 

  6. Cohn ES, Kelley PM, Fowler TW, Gorga MP, Lefkowitz DM, Kuehn HJ, et al. Clinical studies of families with hearing loss attributable to mutations in the connexin 26 gene (GJB2/DFNB1). Pediatrics. 1999;103:546–550

    Article  CAS  Google Scholar 

  7. Liu XZ, Pandya A, Angeli S, Telischi FF, Arnos KS, Nance WE, et al. Audiological features of GJB2 (Connexin 26) deafness. Ear Hear. 2005;26:361–369

    Article  Google Scholar 

  8. Erbe CB, Harris KC, Runge Samuelson CL, Flanary VA, Wackym PA. Connexin 26 and connexin 30 mutations in children with nonsyndromic hearing loss. Laryngoscope. 2004;114:607–611

    Article  CAS  Google Scholar 

  9. Denoyelle F, Mariin S, Weil D, Moatti L, Chauvin P, Garabédian ÉN, et al. Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling. Lancet. 1999;353:1298–1303

    Article  CAS  Google Scholar 

  10. Orzan E, Polli R, Martella M, Vinanzi C, Leonardi M, Murgia A. Molecular genetics applied to clinical practice: the Cx26 hearing impairment. Br J Audiol. 1999; 33: 291–295

    Article  CAS  Google Scholar 

  11. Pampanos A, Economides J, Iliadou V, Neou P, Leotsakos P, Voyiatzis N, et al. Prevalence of GJB2 mutations in prelingual deafness in the Greek population. Int J Pediatr Otorhinolaryngol. 2002;65:101–108

    Article  Google Scholar 

  12. Iliades T, Eleftheriades N, Iliadou V, Pampanos A, Voyiatzis N, Economides J, et al. Prelingual nonsyndromic hearing loss in Greece: molecular and clinical findings. ORL. 2002; 64: 321–323

    Article  CAS  Google Scholar 

  13. Mustafa MW. Prevalence of the connexin-26 mutation 35delG in non-syndromic hearing loss in Egypt. Int J Otorhinolaryngol. 2004; 3: 1

    Google Scholar 

  14. Gazzaz B, Weil D, Raïs L, Akhyat O, Azeddoug H, Nadifi S. Autosomal recessive and sporadic deafness in Morocco: high frequency of the 35delG GJB2 mutation and absence of the 342-kb GJB6 variant. Hear Res. 2005; 210: 80–84

    Article  CAS  Google Scholar 

  15. Ratbi I, Hajji S, Ouldim K, Aboussair N, Feldmann D, Sefiani A. The mutation 35delG of the gene of the connexin 26 is a frequent cause of autosomal-recessive non-syndromic hearing loss in Morocco. Arch Pediatr. 2007; 14: 450–453

    Article  CAS  Google Scholar 

  16. Marlin S, Feldmann D, Blons H, Loundon N, Rouillon I, Albert S, et al. GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort of hearing-impaired patients. Arch Otolaryngol Head Neck Surg. 2005;131:481–487

    Article  Google Scholar 

  17. Medica I, Rudolf G, Prpić I, Stanojević M, Peterlin B. Incidence of the del35G/GJB2 mutation in Croatian newborns with hearing impairment. Med Sci Monit. 2005; 11: CR533–CR535

    CAS  PubMed  Google Scholar 

  18. Neocleous V, Aspris A, Shahpenterian V, Nicolaou V, Panagi C, Ioannou I, et al. High frequency of 35delG GJB2 mutation and absence of del(GJB6-D13S1830) in Greek Cypriot patients with nonsyndromic hearing loss. Genet Test. 2006;10:285–289

    Article  CAS  Google Scholar 

  19. Walsh T, Rayan AA, Sa’ed JA, Shahin H, Shepshelovich J, Lee MK, et al. Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population. Hum Genom. 2006; 2: 203–211

    Article  CAS  Google Scholar 

  20. Meguid NA, Omran MH, Dardir AA, Abdel Raouf ER, Ghorab IA, Abdel Raouf HR, et al. Study of 35delG in congenital sensorineural non-syndromic hearing loss in Egypt. J Appl Sci Res. 2008;4:621–626

    CAS  Google Scholar 

  21. Morell RJ, Kim HJ, Hood LJ, Goforth L, Friderici K, Fisher R, et al. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness. N Engl J Med. 1998;339:1500–1505

    Article  CAS  Google Scholar 

  22. Wilcox SA, Saunders K, Osborn AH, Arnold A, Wunderlich J, Kelly T, et al. High frequency hearing loss correlated with mutations in the GJB2 gene. Hum Genet. 2000;106:399–405

    Article  CAS  Google Scholar 

  23. Hamelmann C, Amedofu GK, Albrecht K, Muntau B, Gelhaus A, Brobby GW, et al. Pattern of connexin 26 (GJB2) mutations causing sensorineural hearing impairment in Ghana. Hum Mutat. 2001;18:84–85

    Article  CAS  Google Scholar 

  24. Gasmelseed NM, Schmidt M, Magzoub MM, Macharia M, Elmustafa OM, Ototo B, et al. Low frequency of deafness-associated GJB2 variants in Kenya and Sudan and novel GJB2 variants. Hum Mutat. 2004;23:206–207

    Article  Google Scholar 

  25. Esmaeili M, Bonyadi M, Nejadkazem M. Common mutation analysis of GJB2 and GJB6 genes in affected families with autosomal recessive non-syndromic hearing loss from Iran: simultaneous detection of two common mutations (35delG/del(GJB6-D13S1830)) in the DFNB1-related deafness. Int J Pediatr Otorhinolaryngol. 2007; 71: 869–873

    Article  Google Scholar 

  26. Al Kandari M, Farid S, Al Shennawi M, Soliman T Epidemiological study of hearing loss among Kuwaiti school children. 1996 Unpublished Master Degree thesis Cairo University

  27. Estivill X, Fortina P, Surrey S, Rabionet R, Melchionda S, D’Agruma L, et al. Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet. 1998;351:394–398

    Article  CAS  Google Scholar 

  28. Rabionet R, Gasparini P, Estivill X. Molecular genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins. Hum Mutat. 2000; 16: 190–202

    Article  CAS  Google Scholar 

  29. Smith R. Genetics of hearing loss. Seminar in sensorineural hearing loss in children. Nat Genet. 2003; 35: 21–23

    Google Scholar 

  30. Gualandi F, Ravani A, Berto A, Sensi A, Trabanelli C, Falciano F, et al. Exploring the clinical and epidemiological complexity of GJB2-linked deafness. Am J Med Genet. 2002;112:38–45

    Article  CAS  Google Scholar 

  31. Engel Yeger B, Zaaroura S, Zlotogora J, Shalev S, Hujeirat Y, Carrasquillo M, et al. The effects of a connexin 26 mutation–35delG–on oto-acoustic emissions and brainstem evoked potentials: homozygotes and carriers. Hear Res. 2002;163:93–100

    Article  CAS  Google Scholar 

  32. Morton CC. Genetics, genomics and gene discovery in the auditory system. Hum Mol Genet. 2002; 11: 1229–1240

    Article  CAS  Google Scholar 

  33. De Brouwer APM, Pennings RJE, Roeters M, Van Hauwe P, Astuto LM, Hoefsloot LH, et al. Mutations in the calcium-binding motifs of CDH23 and the 35delG mutation in GJB2 cause hearing loss in one family. Hum Genet. 2003;112:156–163

    Article  Google Scholar 

  34. Kolkaila E, Emara A, El Sharnooby J. Connexin26 gene mutations in patients with non-syndromic hearing loss and the use of multi-frequency pure tone audiometry. Sci J Med Fac (Girls). 2004; 25: 939–955

    Google Scholar 

  35. Kudo T, Oshima T, Kure S, Matsubara Y, Ikeda K. Mutation detection of GJB2 using IsoCode and real-time quantitative polymerase chain reaction with SYBR green I dye for newborn hearing screening. Laryngoscope. 2004; 114: 1299–1304

    Article  CAS  Google Scholar 

  36. Ramsebner R, Volker R, Lucas T, Hamader G, Weipoltshammer K, Baumgartner WD, et al. High incidence of GJB2 mutations during screening of newborns for hearing loss in Austria. Ear Hear. 2007;28:298–301

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Audiology Unit of ENT Department, Cairo University, 13 Kasrelnil St., Cairo, Egypt

    Ahmed S. Farid, Mohammed I. Shabana & Mona H. Selim

  2. ENT Department, Kuwait University, Kuwait, Kuwait

    Khalid H. Al Sebeih

  3. Sheikh Salem Al-Ali Center for Audiology and Speech, Kuwait University, Kuwait, Kuwait

    Maryam M. Abdulla

Authors
  1. Ahmed S. Farid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammed I. Shabana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mona H. Selim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Khalid H. Al Sebeih
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maryam M. Abdulla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mona H. Selim.

Additional information

Conflicts of interest

There are no conflicts of interest.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Farid, A.S., Shabana, M.I., Selim, M.H. et al. Genetic study of autosomal recessive nonsyndromic sensorineural hearing loss in Kuwaiti children. Egypt J Otolaryngol 28, 35–43 (2012). https://doi.org/10.7123/01.EJO.0000411085.21218.f5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.7123/01.EJO.0000411085.21218.f5

Keywords

  • 35delG
  • auditory brainstem response
  • ARNSNHL
  • connexin26
  • genetic hearing loss
  • pure tone audiometry
  • transient evoked otoacoustic emission