title: Screening of families with autosomal recessive non-syndromic hearing impairment (ARNSHI) for mutations in GJB2 gene: Indian scenario.
abstract: Several studies have reported that mutations in the GJB2 gene (coding for connexin26) are a common cause of recessive non-syndromic hearing impairment. A GJB2 mutant allele, 35delG, has been found to have a high prevalence in most ethnic groups. Though mutations in the GJB2 gene have been shown to cause autosomal recessive deafness in Indian families, the frequencies of the various mutations are still unknown. In the present study, we analyzed 45 Indian families belonging to three different states, namely, Karnataka, Tamil Nadu, and Delhi with non-syndromic hearing impairment and an apparently autosomal recessive mode of inheritance. All the families were initially screened for three mutations (W24X, W77X, and Q124X) by using allele-specific PCR primers; mutations were confirmed by DNA sequencing. Families that were heterozygous or negative for tested mutations of the GJB2 gene were sequenced directly to identify the complementary mutation and other mutations in GJB2. Four families were homozygous for W24X, constituting around 8.8%. In two families, the affected individuals were compound heterozygotes for W24X; one family (DKB16) carried 35delG with W24X while the other family (DKB7) carried R143W with W24X. We suggest that W24X is a common allele among the mutations screened, causing autosomal recessive non-syndromic hearing impairment (ARNSHI) in the Indian population.
authors.affiliation: Genetics Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Manjula
authors.initials: M
authors.lastname: Maheshwari
authors.forename: R
authors.initials: R
authors.lastname: Vijaya
authors.forename: Manju
authors.initials: M
authors.lastname: Ghosh
authors.forename: Shivaram
authors.initials: S
authors.lastname: Shastri
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kabra
authors.forename: P S N
authors.initials: PS
authors.lastname: Menon
mesh_terms: D000483:Alleles; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006580:Genetic Carrier Screening / Q000379:methods; D005820:Genetic Testing / Q000379:methods; D006311:Hearing Disorders / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D009154:Mutation; D009679:Nuclear Family; D010375:Pedigree; D013577:Syndrome
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26