Connexin 26 (GJB2) Mutations Associated with Non-Syndromic Hearing Loss (NSHL)
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.
Sanger sequencing of entire coding region contained in single exon (Exon 2) of GJB2 gene in 15 patients of NSHL.
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.
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.
KeywordsConnexin 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
The authors are grateful to all the participants for their kind contribution to this study.
SM: Conceptualisation, clinical evaluation of patients, data curation, investigation, formal analysis, methodology, validation, writing- original draft; HP and PS: Data curation, conducting laboratory work, formal analysis; KM: Conceptualisation, clinical evaluation of patients, data curation, investigation, methodology, validation, supervision, writing- review and editing; SRP: Conceptualisation, clinical evaluation of patients, funding acquisition, project administration, supervision, writing- review and editing. SRP will act as guarantor for this paper.
Compliance with Ethical Standards
The study has been approved by the Institute Ethics Committee. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional committee.
Conflict of Interest
Shubha R Phadke has received a grant from the Indian Council of Medical Research, Government of India, New Delhi, India (Grant number 63/8/2010-BMS). The other authors declare that they have no conflict of interest.
Source of Funding
This study was funded by Indian Council of Medical Research, Government of India, New Delhi, India (Grant number 63/8/2010-BMS).