Highly Prevalent GJB2 Gene Mutations among Congenital Nonsyndromic Hearing Impairment in a South Indian Population
Hearing impairment (HI) is due to genetic (autosomal recessive) having a frequency of one in 1000 children. Hearing impairment has a widespread gene involvement of various chromosomes. Mutations in the GJB2 gene on chromosome 13 were frequent findings for congenital non-syndromic hearing impairment. To make it more complicated, it has been observed that these mutations show population variations. Objective: To determine the prevalence of the most common mutations in the GJB2 gene among the Indian population. Methods: In this study, 38 subjects (22 cases and 16 controls) enrolled, and the degree of hearing loss was assessed. To identify the involvement of GJB2 gene mutations p.W24X and c.235delC among the populations, PCR Technique and RFLP were adopted. Results: The mutations under investigation were at a higher prevalence rate, i.e., 45.45% for c.235delC and a lower prevalence rate of 18.18% for p.W24X, and both the mutations had heterozygous natures. Conclusion: This paper is the first of this kind that tries to identify a prevalent mutation in the GJB2 gene in the population of Karnataka state. The results are supported to some extent by previous Indian studies involving other than the current population. It is also noteworthy that the mutations identified are heterozygous and, therefore, are not pathogenic. This implies either the existence of potential mutations in the gene’s unexplored region or the possible co-implication of another connexin gene, i.e., the digenic origin of the hearing loss, which could be related to the putative formation of heteromeric connexons or heterotypic channels.
Keywords: congenital nonsyndromic hearing loss, p.W24X, c.235delC mutations.
MEHL A.L., and THOMSON V. Newborn Hearing Screening: The Great Omission. Pediatrics, 1998, 101(1): e4.
MEHL A.L., and THOMSON V. The Colorado Newborn Hearing Screening Project, 1992–1999: On the Threshold of Effective Population-Based Universal Newborn Hearing Screening. Pediatrics, 2002, 109(1): e7.
MORTON N.E. Genetic epidemiology of hearing impairment. Annals of the New York Academy of Sciences, 1991, 630: 16-31.
CRYNS K., ORZAN E., MURGIA A., HUYGEN P.L.M., MORENO F., DEL CASTILLO I., CHAMBERLIN G.P. , AZAIEZ H., PRASAD S., CUCCI R.A., LEONARDI E., SNOECKX R.L., GOVAERTS P.J., VAN DE HEYNING P.H., VAN DE HEYNING C.M., SMITH R.J.H., and VAN CAMP G. A genotype-phenotype correlation for GJB2 (connexin 26) deafness. Journal of Medical Genetics, 2004, 41(3): 147-154.
ESTIVILL X., FORTINA P., SURREY S., RABIONET R., MELCHIONDA S., D’AGRUMA L., MANSFIELD E., RAPPAPORT E., GOVEA N., MILÀ M., ZELANTE L., and GASPARINI P. Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet, 1998, 351(9100): 394-398.
LÖFFLER J., NEKAHM D., HIRST-STADLMANN A., GÜNTHER B., MENZEL H.J., UTERMANN G., and JANECKE A.R. Sensorineural hearing loss and the incidence of Cx26 mutations in Austria. Lancet, 1998, 351(9100): 394-398. DOI: 10.1016/S0140-6736(97)11124-2.
KUDO T, IKEDA K, KURE S, MATSUBARA Y, OSHIMA T, WATANABE K.I., KAWASE T., NARISAWA K., and TAKASAKA T. Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population. American Journal of Medical Genetics, 2000, 90(2): 141-145.
GÜNTHER B., STEINER A., NEKAHM-HEIS D., ALBEGGER K., ZOROWKA P., UTERMANN G., and JANECKE A. The 342-kb deletion in GJB6 is not present in patients with non-syndromic hearing loss from Austria. Human Mutation, 2003, 22(2): 180. DOI: 10.1002/humu.9167.
DEL CASTILLO F.J., RODRÍGUEZ-BALLESTEROS M., ALVAREZ A., HUTCHIN T., LEONARDI E., DE OLIVEIRA C.A., AZAIEZ H., BROWNSTEIN, Z. AVENARIUS M.R., MARLIN S., PANDYA A., SHAHIN H., SIEMERING K.R., WEIL D., WUYTS W., AGUIRRE L.A., MARTÍN Y., MORENO-PELAYO M.A., VILLAMAR M., AVRAHAM K.B., DAHL H.-H.M., KANAAN M., NANCE W.E., PETIT C., SMITH R.J.H., VAN CAMP G., SARTORATO E.L., MURGIA A., MORENO F., and DEL CASTILLO I. A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. Journal of Medical Genetics, 2005, 42(7): 588-594.
YAO J., LU Y., WEI Q., CAO X., and XING G. A systematic review and meta-analysis of 235delC mutation of GJB2 gene. Journal of Translational Medicine, 2012, 10: 136. DOI: 10.1186/1479-5876-10-136.
FROLENKOV G.I., ATZORI M., KALINEC F., MAMMANO F., and KACHAR B. The membrane-based mechanism of cell motility in cochlear outer hair cells. Molecular Biology of the Cell, 1998, 9(8): 1961-1968. DOI: 10.1091/mbc.9.8.1961.
DAHL H.-H.M., TOBIN S.E., POULAKIS Z., RICKARDS F.W., XU X., GILLAM L., WILLIAMS J., SAUNDERS K., CONE-WESSON B., and WAKE M. The contribution of GJB2 mutations to slight or mild hearing loss in Australian elementary school children. Journal of Medical Genetics, 2006, 43(11): 850-855. DOI: 10.1136/jmg.2006.042051.
KELSELL D.P., DI W.L., and HOUSEMAN M.J. Connexin mutations in skin disease and hearing loss. American Journal of Human Genetics, 2001, 68(3): 559-568. DOI: 10.1086/318803.
SCOTT D.A., KRAFT M.L., CARMI R., RAMESH A., ELBEDOUR K., YAIRI Y., SRISAILAPATHY C.R., ROSENGREN S.S., MARKHAM A.F., MUELLER R.F., LENCH N.J., VAN CAMP G., SMITH R.J., and SHEFFIELD V.C. Identification of mutations in the connexin 26 gene that cause autosomal recessive nonsyndromic hearing loss. Human Mutation, 1998, 11(5): 387-394.
RICKARD S., KELSELL D.P., SIRIMANA T., RAJPUT K., MACARDLE B., and BITNER-GLINDZICZ M. Recurrent mutations in the deafness gene GJB2 (connexin 26) in British Asian families. Journal of Medical Genetics, 2001, 38(8): 530-533. DOI: 10.1136/jmg.38.8.530.
RAMSHANKAR M., GIRIRAJAN S., DAGAN O., RAVI SHANKAR H.M., JALVI R., RANGASAYEE R., AVRAHAM K.B., and ANAND A. Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India. Journal of Medical Genetics, 2003, 40(5): e68.
MAHESHWARI M., VIJAYA R., GHOSH M., SHASTRI S., KABRA M., and MENON P.S.N. Screening of families with autosomal recessive non-syndromic hearing impairment (ARNSHI) for mutations in GJB2 gene: Indian scenario. American Journal of Medical Genetics - Part A, 2003, 120A(2): 180-184.
CARHART R., and JERGER J. Preferred method for clinical determination of pure-tone thresholds. Journal of Speech & Hearing Disorders, 1959, 24: 330-345. https://doi.org/10.1044/jshd.2404.330
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