En
Abstract
Aim
The aim of this study was to detect 35delG and 167delT mutations in the connexin 26 gene among Egyptian patients with nonsyndromic sensorineural hearing loss, allowing accurate diagnosis, proper genetic counseling, and carrier detection.
Patients and methods
Fifty-one patients were subjected to 35delG and 167delT mutations detection using PCR-based techniques.
Results
Seven patients had the 35delG mutation. Four patients were homozygous and four patients were heterozygous for this deletion. Two homozygotes were sibs and two heterozygotes were sibs as well. The allelic frequency for 35delG was 10.8%. The 167delT was not detected in any of the patients studied.
Conclusion
The 35delG is a common pathogenic mutation and an important contributor toward autosomal recessive nonsyndromic hearing loss in the Egyptian population.
Article PDF
Similar content being viewed by others
References
Kral A, O’Donoghue GM. Profound deafness in childhood. N Engl J Med 2010; 363: 1438–1450.
Cordeiro-Silva Mde F, Barbosa A, Santiago M, Provetti M, Dettogni RS, Tovar TT, et al. Mutation analysis of GJB2 and GJB6 genes in Southeastern Brazilians with hereditary nonsyndromic deafness. Mol Biol Rep 2011; 38:1309–1313.
Hilgert N, Smith RJ, Van Camp G. Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics? Mutat Res 2009; 681: 189–196.
Martinez AD, Acuna R, Figueroa V, Maripillan J, Nicholson B. Gap-junction channels dysfunction in deafness and hearing loss. Antioxid Redox Signal 2009; 11: 309–322.
Zhao HB, Kikuchi T, Ngezahayo A, White TW. Gap junctions and cochlear homeostasis. J Membr Biol 2006; 209: 177–186.
Da Motta LH, Felix TM, de Souza LT, Lavinsky-Wolff M, Costa-Motta FM, de Faria MR, et al. Prevalence of the 35delG mutation in deaf South Brazilian infants submitted to cochlear implantation. Int J Pediatr Otorhinolaryngol 2012; 76:287–290.
Radulesco L, Mârþu C, Birkenhager R, Cozma S, Ungureanu L, Laszig R. Prevalence of mutations located at the dfnb1 locus in a population of cochlear implanted children in eastern Romania. Int J Pediatr Otorhinolaryngol 2012; 76: 90–94.
Smith RJ, Hone S. Genetic screening for deafness. Pediatr Clin North Am 2003; 50: 315–329.
Smith RJ. Clinical application of genetic testing for deafness. Am J Med Genet 2004; 130A:8–12.
Storm K, Willocx S, Flothmann K, Van Camp G. Determination of the carrier frequency of the common GJB2 (connexin-26) 35delG mutation in the Belgian population using an easy and reliable screening method. Hum Mutat 1999; 14: 263–266.
Bors A, Andrikovics H, Kalmar L, Erdei N, Galambos S, Losonczi A, et al. Frequencies of two common mutations (c.35delG and c.167delT) of the connexin 26 gene in different populations of Hungary. Int J Mol Med 2004; 14:1105–1108.
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.
Chan DK, Schrijver I, Chang KW. Diagnostic yield in the workup of congenital sensorineural hearing loss is dependent on patient ethnicity. Otol Neurotol 2011; 32: 81–87.
Snoeckx RL, Hassan DM, Kamal NM, Van Den Bogaert K, Van Camp G. Mutation analysis of the GJB2 (connexin 26) gene in Egypt. Hum Mutat 2005; 26:60–61.
Abdel-Meguid N, Omran MH, Dardir AA, Abdel-Raouf ER, Ghorab IA, et al. Study of 35delG in congenital sensorineural non-syndromic hearing loss in Egypt. J Appl Sci Res 2008; 4:621–626.
Mohamed MR, Alesutan I, Föller M, Sopjani M, Bress A, Baur M, et al. Functional analysis of a novel I71N mutation in the GJB2 gene among Southern Egyptians causing autosomal recessive hearing loss. Cell Physiol Biochem 2010; 26:959–966.
Evirgen N, Solak M, Derekoy S, Erdogan M, Yildiz H, Eser B, et al. Genotyping for Cx26 and Cx30 mutations in cases with congenital hearing loss. Genet Test 2008; 12:253–256.
Mahasneh AA, Battah RM. Prevalence of connexin 26 mutations in patients from Jordan with non syndromic hearing loss. Int J Hum Genet 2006; 6: 119–124.
Shahin H, Walsh T, Sobe T, Lynch E, King MC, Avraham KB, et al. Genetics of congenital deafness in the Palestinian population: multiple connexin 26 alleles with shared origins in the Middle East. Hum Genet 2002; 110:284–289.
Gazzaz B, Weil D, Rais 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.
Trabelsi M, Bahri W, Habibi M, Zainine R, Maazoul F, Ghazi B, et al. GJB2 and GJB6 screening in Tunisian patients with autosomal recessive deafness. Int J Pediatr Otorhinolaryngol 2013; 77:714–716.
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.
Murgia A, Orzan E, Polli R, Martella M, Vinanzi C, Leonardi E, et al. Cx26 deafness: mutation analysis and clinical variability. J Med Genet 1999; 36:829–832.
Gabriel H, Kupsch P, Sudendey J, Winterhager E, Jahnke K, Lautermann J. Mutations in the connexin26/GJB2 gene are the most common event in non-syndromic hearing loss among the German population. Hum Mutat 2001; 17: 521–522.
Joseph AY, Rasool TJ. High frequency of connexin26 (GJB2) mutations associated with nonsyndromic hearing loss in the population of Kerala, India. Int J Pediatr Otorhinolaryngol 2009; 73: 437–443.
Lee KY, Choi SY, Bae JW, Kim S, Chung KW, Drayna D, et al. Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients. Int J Pediatr Otorhinolaryngol 2008; 72:1301–1309.
Denoyelle F, Weil D, Maw MA, Wilcox SA, Lench NJ, Allen-Powell DR, et al. Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene. Hum Mol Genet 1997; 6:2173–2177.
Van Laer L, Coucke P, Mueller RF, Caethoven G, Flothmann K, Prasad SD, et al. A common founder for the 35delG GJB2 gene mutation in connexin 26 hearing impairment. J Med Genet 2001; 38:515–518.
Watterson GA, Guess HA. Is the most frequent allele the oldest? Theor Popul Biol 1977; 11: 141–160.
Lucotte G. High prevalences of carriers of the 35delG mutation of connexin 26 in the Mediterranean area. Int J Pediatr Otorhinolaryngol 2007; 71: 741–746.
Janecke AR, Hirst-Stadlmann A, Günther B, Utermann B, Müller T, Löffler J, et al. Progressive hearing loss, and recurrent sudden sensorineural hearing loss associated with GJB2 mutations — phenotypic spectrum and frequencies of GJB2 mutations in Austria. Hum Genet 2002; 111:145–153.
Lazar C, Popp R, Trifa A, Mocanu C, Mihut G, Al-Khzouz C, et al. Prevalence of the c.35delG and p.W24X mutations in the GJB2 gene in patients with nonsyndromic hearing loss from North-West Romania. Int J Pediatr Otorhinolaryngol 2010; 74:351–355.
Sansovic I, Knezevic J, Musani V, Seeman P, Barisic I, Pavelic J. GJB2 mutations in patients with nonsyndromic hearing loss from Croatia. Genet Test Mol Biomarkers 2009; 13: 693–699.
Lerer I, Sagi M, Malamud E, Levi H, Raas-Rothschild A, Abeliovich D. Contribution of connexin 26 mutations to nonsyndromic deafness in Ashkenazi patients and the variable phenotypic effect of the mutation 167delT. Am J Med Genet 2000; 95: 53–56.
Brownstein Z, Avraham KB. Deafness genes in Israel: implications for diagnostics in the clinic. Pediatr Res 2009; 66: 128–134.
Prasad S, Cucci RA, Green GE, Smith RJ. Genetic testing for hereditary hearing loss: connexin 26 (GJB2) allele variants and two novel deafness-causing mutations (R32C and 645–648delTAGA). Hum Mutat 2000; 16: 502–508.
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Conflicts of interest
None declared.
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/.
About this article
Cite this article
El Barbary, N.E., El Belbesy, M.F., Asal, S.I. et al. Detection of 35delG, 167delT mutations in the connexin 26 gene among Egyptian patients with nonsyndromic sensorineural hearing loss. Egypt J Otolaryngol 31, 42–46 (2015). https://doi.org/10.4103/1012-5574.152707
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.4103/1012-5574.152707