Low prevalence of DFNB1 (connexin 26) mutations in British Pakistani children with non-syndromic sensorineural hearing loss

Objective To determine the clinical sensitivity of DFNB1 genetic testing (analysis of the connexin 26 gene GJB2) for non-syndromic sensorineural hearing loss (SNHL) in British Pakistani children and extend to a comparison with British White children and literature data. Design Retrospective cohort study. Setting City of Bradford, UK. Patients Overall, 177 children (152 families) were eligible; 147 children (123 families) were British Pakistani, and 30 children (29 families) were British White. Interventions DFNB1 testing was offered. Main outcome measures Detection rate for pathogenic bi-allelic GJB2 mutations. Results DFNB1 testing yielded positive results in 6.9% British Pakistani families compared with 15.4% British White families. Of 65 British Pakistani children tested (from 58 families), five children (from four families) were found to be homozygous for the common South Asian GJB2 mutation p. Trp24X. Of 14 British White children tested (from 13 families), bi-allelic pathogenic GJB2 mutations were seen in two children (from two families). Conclusions The contribution of DFNB1 to non-syndromic SNHL in the Bradford British Pakistani children appears to be low when compared with a White peer group and White populations in general. The high prevalence of genetic deafness in this community, attributed to family structure and immigration history, points to a dilution effect in favour of other recessive deafness genes/loci.