Profile of Iranian GJB2 Mutations in Young Population with Novel Mutation

Document Type : Original Article


1 Department and Research Center of ENT & Head and Neck Surgery of Tehran University of Medical Sciences, Tehran, Iran

2 National Institute for Genetic Engineering and Biotechnology, Tehran, Iran

3 Tehran welfare Organization, Tehran, Iran


Despite the enormous heterogeneity of genetic hearing loss, most non-syndromic hearing losses are caused by mutations in the GJB2 gene. We aimed to characterize the mutation profiles of 100 Iranian deaf patients that were under 10 years old.
Materials and Methods
Patients were tested with direct sequencing of entire coding region of the GJB2 gene.
Eight known mutations plus one novel (358delGAG) were found in 25% of study group. The 35delG mutation (64%) constituted the majority of GJB2 mutations.
Role of GJB2 mutation in Iranian young deaf population is more prominent than previous study that can be a result of higher consanguine marriage in population. But our result shows that there is only 25% non- syndromic hearing loss due to high frequency of consanguine marriage in Iranian population. Identification of other genes involved in genetic deafness will help us understand the fundamental mechanisms of normal hearing, both in early diagnosis and therapy.


1.  Kalay  E,  Caylan  R,  Kremer  H,  de  Brouwer  AP,  Karaguzel  A. GJB2  mutations  in  Turkish  patients  with ARNSHL: prevalence and two novel mutations. Hear Res  2005; 203:88-93.
2. Petersen MB, Willems PJ. Non-syndromic, autosomal-recessive deafness. Clin Genet 2006; 69:371-392.
4. Green GE, Scott DA, McDonald JM, Woodworth GG, Sheffield VC, Smith RJ. Carrier rates in the Midwestern United States for GJB2 mutations causing inherited deafness. JAMA 1999; 281:2211-2216.
5. Guilford P, Ben Arab S, Blanchard S, Levilliers J, Weissenbach J, Belkahia A, et al. A non-syndrome form of neurosensory, recessive deafness maps to the pericentromeric region of chromosome 13q. Nat Genet 1994; 6:24-28.
6. 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; 387:80-83.
7. Schrijver I. Hereditary non-syndromic sensorineural hearing loss: transforming silence to sound. J Mol Diagn 2004; 6:275-284.
8. Kelley PM, Cohn E, Kimberling WJ. Connexin 26: required for normal auditory function. Brain Res Brain Res Rev  2000; 32:184-188.
9. Kikuchi T, Kimura RS, Paul DL, Takasaka T, Adams JC. Gap junction systems in the mammalian cochlea. Brain Res Brain Res Rev  2000; 32:163-166.
10. 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.
11. Saadat M, Ansari-Lari M, Farhud DD. Consanguineous marriage in Iran. Ann Hum Biol  2004; 31:263-269.
12. Hashemzadeh chaleshtori M, Farhud D. Familial and sporadic GJB2- related deafness in iran:Review of Gene Mutations. Iran J Publ Health  2007; 36:1-14.
13. Najmabadi H, Nishimura C, Kahrizi K, Riazalhosseini Y, Malekpour M, Daneshi A, et al. GJB2 mutations: passage through Iran. Am J Med Genet A 2005; 133A:132-137.
14. Kelley PM, Harris DJ, Comer BC, Askew JW, Fowler T, Smith SD, et al. Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss. Am J Hum Genet 1998; 62:792-799.
15. Hamid M, Karimipoor M, Chaleshtori MH, Akbari MT. A novel 355-357delGAG mutation and frequency of connexin-26 (GJB2) mutations in Iranian patients. J Genet 2009; 88:359-362.