Shivani Mishra1, Himani Pandey1, Priyanka Srivastava1, Kausik Mandal2, Shubha R Phadke1. 1. Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India. 2. Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India. mandal.kausik@gmail.com.
Abstract
OBJECTIVE: To determine the prevalence and spectrum of Connexin 26 (GJB2) mutations in pre-lingual non-syndromic hearing loss (NSHL) patients in authors' centre and to review the data of Indian patients from the literature. METHODS: Sanger sequencing of entire coding region contained in single exon (Exon 2) of GJB2 gene in 15 patients of NSHL. RESULTS: GJB2 mutations were found in 40% (6/15) of NSHL patients, out of which mono-allelic were 33.3% (2/6). Bi-allelic GJB2 mutations were identified in 4 of 6 patients. Most common GJB2 mutation identified was c.71G > A(p.W24X), comprising 30% of the total GJB2 mutant alleles. Six studies involving 1119 patients with NSHL were reviewed and 4 of them have reported c.71G > A(p.W24X) as the commonest mutation while 2 studies found c.35delG as the commonest. GJB2 mutations accounted for 10.9%-36% cases of NSHL. Sixteen other mutations in GJB2 gene were reported in Indian patients out of which 6 mutations other than c.71G > A(p.W24X) viz., c.35delG, c.1A > G(p.M1V), c.127G > A(p.V43 M), c.204C > G(p.Y86X), c.231G > A(p.W77X) and c.439G > A(p.E147K) were identified in the present study. CONCLUSIONS: Connexin 26 (GJB2) mutations are responsible for 19.4% of NSHL in Indian population. The c.71G > A(W24X) and c.35delG were the most prevalent GJB2 mutations accounting for 72.2% (234 of 324 total mutated alleles from 7 studies) and 15.4% (50 of 324 total mutated alleles from 7 studies) respectively. Thus, screening of these two common mutations in GJB2 gene by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) would greatly help in providing easy genetic diagnosis and help in genetic counseling of the families with NSHL.
OBJECTIVE: To determine the prevalence and spectrum of Connexin 26 (GJB2) mutations in pre-lingual non-syndromic hearing loss (NSHL) patients in authors' centre and to review the data of Indian patients from the literature. METHODS: Sanger sequencing of entire coding region contained in single exon (Exon 2) of GJB2 gene in 15 patients of NSHL. RESULTS:GJB2 mutations were found in 40% (6/15) of NSHL patients, out of which mono-allelic were 33.3% (2/6). Bi-allelic GJB2 mutations were identified in 4 of 6 patients. Most common GJB2 mutation identified was c.71G > A(p.W24X), comprising 30% of the total GJB2 mutant alleles. Six studies involving 1119 patients with NSHL were reviewed and 4 of them have reported c.71G > A(p.W24X) as the commonest mutation while 2 studies found c.35delG as the commonest. GJB2 mutations accounted for 10.9%-36% cases of NSHL. Sixteen other mutations in GJB2 gene were reported in Indian patients out of which 6 mutations other than c.71G > A(p.W24X) viz., c.35delG, c.1A > G(p.M1V), c.127G > A(p.V43 M), c.204C > G(p.Y86X), c.231G > A(p.W77X) and c.439G > A(p.E147K) were identified in the present study. CONCLUSIONS:Connexin 26 (GJB2) mutations are responsible for 19.4% of NSHL in Indian population. The c.71G > A(W24X) and c.35delG were the most prevalent GJB2 mutations accounting for 72.2% (234 of 324 total mutated alleles from 7 studies) and 15.4% (50 of 324 total mutated alleles from 7 studies) respectively. Thus, screening of these two common mutations in GJB2 gene by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) would greatly help in providing easy genetic diagnosis and help in genetic counseling of the families with NSHL.
Entities:
Keywords:
Connexin 26; Gap junction beta 2 (GJB2) gene; Indian population; Non-syndromic hearing loss (NSHL); Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP); Sanger sequencing
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