Genetic contribution of GJB2 gene to hearing impairment in Pakistan

Hamna Tariq, Kalsoom Zaigham, Samra Kousar, Aysha Azhar

Abstract


Background: Hearing impairment (HI) is defined as inability to hear and is an extremely heterogeneous genetic disorder. HI is divided into syndromic (if associated with clinical manifestation in addition to hearing impairment) and non-syndromic forms. So far one hundred and seventeen loci/genes have been mapped for non-syndromic HI and mutations in DFNB1 locus (GJB2 gene) are the most prevalent cause among them. This study was intended to find the relative contribution of the DFNB1 locus/ GJB2 gene for hearing loss in Pakistan and Azad Kashmir.

Methods: Twenty-one families were collected from different rural and urban regions of Pakistan and Azad Kashmir. The contribution of GJB2 gene was initially studied by linkage analysis using short tandem repeats (STR) microsatellite markers. Sanger sequencing was employed to identify the causative variants in coding region of the gene.

Results: Phenotype of four families were found linked with GJB2 gene and all affected individuals of these families segregating same mutation c.231G>A (p.Trp77*) which was confirmed after Sanger sequencing.

Conclusion: The genetic causes of hearing impairment were studied in twenty one families segregating autosomal recessive pattern of inheritance with different ethnicities. We further established the founder effect for the one recurrent mutation in GJB2 gene in Pakistani and Kashmiri hearing impaired families for the very first time.

Keywords: DFNB1; GJB2; Hearing impairment; Pakistan and Kashmir


Full Text:

PDF

References


Petit C. Usher syndrome: from genetics to pathogenesis. Annual Reviews of Genomics and Human Genetics, (2001); 2271-297.

Tabatabaiefar M, Alasti F, Zohour MM, Shariati L, Farrokhi E, et al. Genetic Linkage Analysis of 15 DFNB Loci in a Group of Iranian Families with Autosomal Recessive Hearing Loss. Iranian journal of public health, (2011); 40(2): 34-48.

Rehman AU, Friedman TB, Griffith AJ. Unresolved questions regarding human hereditary deafness. Oral Disease, (2017); 23(5): 551-558.

Hussain R, Bittles AH. The prevalence and demographic characteristics of consanguineous marriages in Pakistan. Journal of Biosocial Science, (1998); 30(2): 261-275.

Yan D, Kannan-Sundhari A, Vishwanath S, Qing J, Mittal R, et al. The Genetic Basis of Nonsyndromic Hearing Loss in Indian and Pakistani Populations. Genetic Testing and Molecular Biomarkers, (2015); 19(9): 512-527.

Van Laer L, Coucke P, Mueller RF, Caethoven G, Flothmann K, et al. A common founder for the 35delG GJB2 gene mutation in connexin 26 hearing impairment. Journal of Medical Genetics, (2001); 38(8): 515-518.

Kudo T, Ikeda K, Kure S, Matsubara Y, Oshima T, et al. Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population. American Journal of Medicine Genetics, (2000); 90(2): 141-145.

Morell RJ, Kim HJ, Hood LJ, Goforth L, Friderici K, et al. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness. New England Journal of Medicine, (1998); 339(21): 1500-1505.

Hwa HL, Ko TM, Hsu CJ, Huang CH, Chiang YL, et al. Mutation spectrum of the connexin 26 (GJB2) gene in Taiwanese patients with prelingual deafness. Genetics in Medicine, (2003); 5(3): 161-165.

Grimberg J, Nawoschik S, Belluscio L, McKee R, Turck A, et al. A simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucleic Acids Research, (1989); 17(20): 8390.

Friedman TB, Griffith AJ. Human nonsyndromic sensorineural deafness. Annual Review of Genomics and Human Genetics, (2003); 4341-402.

Santos RLP, Wajid M, Pham TL, Hussan J, Ali G, et al. Low prevalence of Connexin 26 (GJB2) variants in Pakistani families with autosomal recessive non-syndromic hearing impairment. Clinical Genetics, (2005); 67(1): 61-68.

Shafique S, Siddiqi S, Schraders M, Oostrik J, Ayub H, et al. Genetic spectrum of autosomal recessive non-syndromic hearing loss in Pakistani families. PLoS ONE, (2014); 9(6): e100146.

Yao J, Lu Y, Wei Q, Cao X, Xing G. A systematic review and meta-analysis of 235delC mutation of GJB2 gene. Journal of Translation Medicine, (2012); 10136.


Refbacks

  • There are currently no refbacks.