Hearing impairment is the most common sensory deficit in humans affecting 1 in 1000 newborns. When present in an infant, deafness may have dramatic effects on language acquisition, seriously compromising the quality of their life. Deafness is influenced by both genetic and environmental factors, with inherited causes as the most prominent etiological factor in deafness in developed countries. The genetic basis of hearing loss is complex with numerous loci and genes underlying hereditary sensoryneural non syndromic hearing loss (NSHL) in humans. Despite the wide functional heterogeneity of the genes, mutations in the GJB2 gene are found to be the most common cause of sporadic and recessive NSHL in many populations worldwide. Molecular characterization of deafness in the Republic of Macedonia was performed in 130 NSHL profoundly deaf children from different ethnic origins. Molecular studies included direct sequencing of the GJB2 gene and specific polymerase chain reaction (PCR) analyses for the del(GJB6- D13S1830) mutation. Five common mitochondrial DNA (mtDNA) mutations [A1555G, 961delT+ C(n), T1095C, C1494T and A827G] were also analyzed using the SNaPShot method. In preliminary studies, GJB2 gene mutations were found in 36.4% of analyzed patients, with predominance of 35delG in Macedonian and Albanian patients and W24X in Gypsy patients, respectively. No del(GJB6- D13S1830) mutation was found. None of the analyzed deafness-associated mutations in mtDNA were identified in the studied patients
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1. Cohen MM, Gorlin RJ. Epidemiology, etiology and genetic patterns. In: Gorlin RJ, Toriello HV, Cohen MM, Eds. Hereditary Hearing Loss and Its Syndromes. Oxford: Academic Press. 1995: 9-21.
2. Schrijver I. Hereditary non-syndromic sensorineural hearing loss. Transforming silence to sound. J Molec Diagn. 2004; 6(4): 275-284.
3. Petit C. From deafness genes to hearing mechanisms: harmony and counterpoint. Trends Mol Med. 2006; 12(2): 57-64.
4. Mese G, Londin E, Mui R, Brink PR, White TW. Altered gating properties of functional Cx26 mutants associated with recessive non-syndromic hearing loss. Hum Genet. 2004; 115(3): 191-199.
5. Rabionet R, Zelante L, Lopez-Bigas N, et al. Molecular basis of childhood deafness resulting from mutations in the GJB2 (Connexin 26) gene. Hum Genet. 2000; 106(1): 40-44.
6. Kennenson A, Van Naarden Brown K, Boyle C. GJB2 (Connexin 26) variants and nonsyndromic sensorineural hearing loss: A HuGE review. Genet Med. 2002; 4(4): 258-274.
7. Zelante I, Gasparini P, Estivill X, et al. Connexin 26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Hum Mol Genet. 1997; 6(9): 1605-1609.
8. Morell RJ, Kim HJ, Hood LJ, et al. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness. N Engl J Med. 1998; 339(21): 1500-1505.
9. Abe S, Kelly PM, Kimberling WJ, Usami SI. Connexin 26 gene (GJB2) mutation modulates the severity of hearing loss associated with the 1555A>G mitochondrial mutation. Am J Med Genet. 2001; 103(4): 334-338.
10. Sukarova Stefanovska E, Momirovska A, Cakar M, Efremov GD. GJB2 mutations in non syndromic hearing loss in the Republic of Macedonia. Balkan J Med Genet. 2009; 12(2): 11-17.
11. Del Castillo I, Villamar M, Moreno-Pelayo MA, etal. A deletion involving the connexion 30 gene in nonsyndromic hearing impairment. N Engl J Med. 2002; 346(4): 243-249.
12. Del Castillo I, Moreno-Pelayo MA, Del Castillo FJ, et al. Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multi-center study. Am J Hum Genet. 2003; 73(6): 1452-1458.
13. Maniglia LP, Bruna Moreira CL, Menezes da Silva MA, Piatto VB, Maniglia JV. Screening of the mitochondrial A1555G mutation in patients with sensorineural hearing loss. Rev Bras Otorinolaryngol. 2008; 74(5): 731-736.
14. Bardien S, Human H, Harris T, et al. A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness. BMC Med Genet. 2009; 10: 2.