title: Spectrum and frequency of GJB2, GJB6 and SLC26A4 gene mutations among nonsyndromic hearing loss patients in eastern part of India.
abstract: Genetically caused nonsyndromic hearing loss is highly heterogeneous. Inspite of this large heterogeneity, mutations in the genes GJB2, GJB6 and SLC26A4 are major contributors. The mutation spectrum of these genes varies among different ethnic groups. Only a handful of studies focused on the altered genetic signature of these genes in different demographic regions of India but never focused on the eastern part of the country. Our study for the first time aimed to characterize the mutation profile of these genes in hearing loss patients of West Bengal state, India. Mutations in GJB2, GJB6 and SLC26A4 genes were screened by bidirectional sequencing from 215 congenital nonsyndromic hearing loss patients. Radiological diagnosis was performed in patients with SLC26A4 mutations by temporal bone CT scan. The study revealed that 4.65% and 6.97% patients had monoallelic and biallelic GJB2 mutations respectively. Six mutations were identified, p.W24X being the most frequent one accounting for 71.05% of the mutated alleles. Mutations in GJB6 including the previously identified deletion mutation (GJB6-D13S1830) were not identified in our study. Further, no patients harbored biallelic mutations in the SLC26A4 gene or the common inner ear malformation Enlarged Vestibular Aqueduct (EVA). The mutation profile of GJB2 in our study is distinct from other parts of India, suggesting that the mutation spectrum of this gene varies with ethnicity and geographical origin. The absence of GJB6 mutations and low frequency of SLC26A4 mutations suggest that additional genetic factors may also contribute to this disease.
authors.affiliation: Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700 019, West Bengal, India.
authors.forename: Bidisha
authors.initials: B
authors.lastname: Adhikary
authors.affiliation: Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700 019, West Bengal, India.
authors.forename: Sudakshina
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700 019, West Bengal, India.
authors.forename: Silpita
authors.initials: S
authors.lastname: Paul
authors.affiliation: Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700 019, West Bengal, India.
authors.forename: Biswabandhu
authors.initials: B
authors.lastname: Bankura
authors.affiliation: Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700 019, West Bengal, India.
authors.forename: Arup Kumar
authors.initials: AK
authors.lastname: Pattanayak
authors.affiliation: Department of E.N.T., Institute of Post Graduate Medical Education & Research, 244 A J C Bose Road, Kolkata 700 020, West Bengal, India.
authors.forename: Subhradev
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700 019, West Bengal, India.
authors.forename: Biswanath
authors.initials: B
authors.lastname: Maity
authors.affiliation: Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700 019, West Bengal, India. Electronic address: madhuzoo@yahoo.com.
authors.forename: Madhusudan
authors.initials: M
authors.lastname: Das
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003638:Deafness / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D015995:Prevalence; D000076988:Sulfate Transporters
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26
keywords: Biallelic mutation; GJB2; GJB6; Nonsyndromic hearing loss; SLC26A4