Non-Syndromic Autosomal Recessive Deafness in Gaza Strip: A Study of Five GJB2 Gene Mutations
International Journal of Genetics and Genomics
Volume 2, Issue 5, October 2014, Pages: 92-96
Received: Nov. 5, 2014;
Accepted: Nov. 12, 2014;
Published: Nov. 20, 2014
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Badria F. Essammak, Faculty of Medicine, The Islamic University of Gaza, Palestine
Mohammed J. Ashour, Department of Medical Laboratory Sciences, Faculty of Health Sciences, The Islamic University of Gaza, Palestine
Fadel A. Sharif, Department of Medical Laboratory Sciences, Faculty of Health Sciences, The Islamic University of Gaza, Palestine
Hearing loss is a common, pan-ethnic and highly heterogeneous sensory disorder with an incidence of around 1 in 1000 infants. Genetic causes are thought to be responsible for more than 60% of the cases with the majority of non-syndromic hearing impairment being inherited in an autosomal recessive pattern. The gene that is most frequently mutated in autosomal recessive non-syndromic hearing loss (ARNSHL) is gap junction protein beta-2 (GJB2) which codes for connexin 26 (Cx26). Cx26 plays a key role in potassium homeostasis, which is essential for sound transduction. The aim of this study was to determine the common GJB2 gene mutations in 70 patients suffering from ARNSHL in Gaza strip. The patients were screened for five GJB2 gene mutations namely, c.35delG, c.167delT, c.-23+1G>A, c.229T>C (p.Trp77Arg) and c.235delC. Study results revealed that GJB2 mutations account for at least 35.7% of the ARNSHL with mutant allele frequency of 0.4%. The most frequently encountered mutation was c.35delG which accounted for 35.7% of the ARNSHL cases in either homozygous (34.3%) or heterozygous (1.4%) form and represented about 80.5% of all the detected mutations. The second most frequent mutation was c.235delC which was found only in heterozygous form. The third mutation was c.-23+1G>A which was identified in only one subject (1.4%) in a compound heterozygous form along with c.35delG. The c.167delT and p.Trp77Arg mutations were not observed in our patients. We conclude that there is a significant contribution of GJB2 mutations to congenital ARNSHL in the Palestinian population of Gaza strip. Screening for GJB2 mutations particularly, c.35delG, c.235delC and c.-23+1G>A should be offered to ARNSHL patients to confirm diagnosis of their congenital deafness, to deliver proper genetic counseling for the affected individuals and their families and to help them benefit from prenatal and pre-implantation genetic diagnosis.
Badria F. Essammak,
Mohammed J. Ashour,
Fadel A. Sharif,
Non-Syndromic Autosomal Recessive Deafness in Gaza Strip: A Study of Five GJB2 Gene Mutations, International Journal of Genetics and Genomics.
Vol. 2, No. 5,
2014, pp. 92-96.
Abe S, Usami SH, Shinkawa H, Kelley PM, Kimberling WJ. Prevalent connexin 26 gene (GJB2) mutations in Japanese. J Med Genet 2000, 37:41–43.
Al-Achkar W, Moassass F, Al-Halabi B, Al-Ablog A. Mutations of the Connexin 26 gene in families with non-syndromic hearing loss. Molecular Medicine Reports 2011, 4: 331-335.
Al-Qahtani MH, Baghlab I, Chaudhary AG, Abuzenadah AM, Bamanie A, Daghistani KJ, et al. A. Spectrum of GJB2 Mutations in a Cohort of Non-syndromic Hearing Loss Cases from the Kingdom of Saudi Arabia. Genetic Testing and Molecular Biomarkers 2010, 14(1):79-83.
Bonyadi M, Fotouhi N, Esmaeili M. Prevalence of IVS1+1G>A mutation among Iranian Azeri Turkish patients with autosomal recessive non-syndromic hearing loss (ARNSHL). International Journal of Pediatric Otorhinolaryngology 2011, 75: 1612-1615.
Chan DK and Chang KW. GJB2-Associated Hearing Loss: Systematic Review of Worldwide Prevalence, Genotype, and Auditory Phenotype. Laryngoscope 2013, 124(2): E34-53.
Cifuentes L, Arancibia M, Torrente M, Acuña M, Farfán C, Ríos C. Prevalence of the 35delG mutation in the GJB2 gene in two samples of non-syndromic deaf subjects from Chile. Biol. Res. 2013: 46(3) Santiago.
Falah M, Houshmand M, Akbaroghli S, Mahmodian S, Ghavami Y, Farhadi M. Profile of Iranian GJB2 Mutations in Young Population with Novel Mutation. Iranian Journal of Basic Medical Sciences 2011, 14 (3): 213-218.
Freitas Cordeiro-Silva M, Barbosa A, Santiago M, Provetti M, Rabbi- Bortolini E. Prevalence of 35delG/GJB2 and del (GJB6-D13S1830) mutations in patients with non-syndromic deafness from a population of Espírito Santo – Brazil. Braz J Otorhinolaryngol 2010, 76(4):428-32.
Gaffar M, Budu, Kuhuwael FG, Yusuf I. A Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) Analysis of Connexin 26 (GJB2) Gene Common Mutation (235delC) In Indonesian Patients with Prelingual Non-syndromic Sensorineural Hearing Loss: A Preliminary Study. The Open Otorhinolaryngology Journal 2009, 3, 16-20.
Gandía M, del Castillo FJ, Rodríguez-Álvarez FJ, Garrido G, Villamar M., Calderón M, et al. A Novel Splice-Site Mutation in the GJB2 Gene Causing Mild Postlingual Hearing Impairment. PLoS ONE 2013, 8(9): e73566.
Ibrahim SM, Ali M, Ahmad S, Ali L, Muhammad N, Tareen R, et al. Autosomal Recessive Deafness is Heterogeneous in Pakistani Pakhtun Population. Curr. Res. J. Biol. Sci. 2011, 3(1): 17-24.
Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 1997, 387 (6628): 80-83.
Kenneson A, Naarden Braun KV, Boyle C. GJB2 (connexin 26) variants and non-syndromic sensorineural hearing loss: A HuGE review. Genet Med. 2002, 4 (4): 258–274.
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. Clinical Genetics 2004, 65(6): 506-508.
Mahyari ZN and Monem FS, GJB2 gene mutations in Syrians with sensorineural hearing loss. Middle East Journal of Medical Genetics 2012, 1(2):80-84.
Matsunaga T. Value of genetic testing in the ontological approach for sensorineural hearing loss. Keio J Med 2009, 58 (4): 216－222.
Medlej-Hashim M, Mustapha M, Chouery E, Weil D, Parronaud J, Salem N, Delague V et al. Non-syndromic recessive deafness in Jordan: mapping of a new locus to chromosome 9q34.3 and prevalence of DFNB1 mutations. European Journal of Human Genetics 2002, 10: 391-394.
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 Non-syndromic Recessive Deafness. The New England Journal of Medicine 1998, 339 (21): 1500-1505.
Mukherjee M, Phadke SR, and Mittal B. Connexin 26 and autosomal recessive non-syndromic hearing loss. Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India 2003, 9 (2): 40-50.
Mustapha M, Salem N, Delague V, Chouery E, Ghassibeh M, Rai M, Loiselet J et al. Autosomal recessive non-syndromic hearing loss in the Lebanese population: prevalence of the 30delG mutation and report of two novel mutations in the connexin 26 (GJB2) gene. J Med Genet 201, 38: e36.
Padma G, Ramchander PV, Nandur UV, Padma T. GJB2 and GJB6 gene mutations found in Indian probands with congenital hearing impairment. Journal of Genetics 2009, 88( 3): 267–272.
Perea Y, Mato J, Amores I, Ferreira R. Study of six mutations in the GJB2 gene in Cuban patients with non-syndromic sensorineural deafness. Biotecnología Aplicada 2007, 24:241-245.
RamShankar M, Girirajan S, Dagan O, Ravi Shankar HM, Jalvi R, Rangasayee R, Avraham KB , Anand A. Contribution of connexin 26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India. J Med Genet 2003, 40:e68.
Riahi Z, Hammami H, Ouragini H, Messai H, Zainine R, Bouyacoub Y, et al. Update of the spectrum of GJB2 gene mutations in Tunisian families with autosomal recessive non-syndromic hearing loss. Gene 2013, 525(1):1-4.
Rodríguez-Paris J, Tamayo ML, Gelvez N, Schrijver I. Allele-Specific Impairment of GJB2 Expression by GJB6 Deletion del(GJB6-D13S1854). PLoS ONE 2011, 6(6): e21665.
Scott DA, Kraft ML. Carmi R, Ramesh A, Elbedour K, Yairi Y, et al. Identification of mutations in the connexin 26 gene that cause autosomalrecessive non-syndromic hearing loss. Hum Mutat, 1998, 11(5):387-394.
Seeman, P. and Sakmaryova, I. (2006). High prevalence of the IVS1-1G to A/GJB2 mutation among Czech hearing impaired patients with monoallelic mutation in the coding region of the GJB2. Clin Genet, 69: 410 – 413.
Shahin H, Walsh T, Sobe T, Lynch E, Claire KM, 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.
Sirmaci A, Akcayoz-Duman D, Tekin M. The c.IVS1+1G>A mutation in the GJB2 gene is prevalent and large deletions involving the GJB6 gene are not present in the Turkish population. J Genet 2006, 85:213-216.
Snoeckx RL, Hassan DM, Kamal NM, Den Bogaert KV, Camp GV. Mutation Analysis of the GJB2 (Connexin 26) Gene in Egypt. Human Mutation 2005, 26 (1): 60-61.
Tang HY, Fang P, Ward PA, Schmitt E, Darilek S, Manolidis S, et al. DNA sequence analysis of GJB2, encoding connexin 26: Observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls. Am J Med Genet Part A 2006, 140A:2401–2415.
Toth T, Kupka S, Haack B, Fazakas F, Muszbek L, et al. Coincidence of mutations in different connexin genes in Hungarian patients. Int J Mol Med 2007, 20: 315–321.