Screening for autosomal recessive non-syndromic deafness: The Indian story
Approximately 1/1000 live born are affected by severe to profound deafness at birth or during early childhood. In developed countries, about 50-60% of deaf individuals without an obvious environmental origin have a genetic basis. Autosomal recessive inheritance contributes to 75-80% of prelingual, bilateral non-syndromic hearing loss of genetic etiology (DFNB) and half of them are attributed to homozygous mutations in GJB2 gene worldwide. Although hearing impairment is an important health problem and consanguineous marriages are not very uncommon, data on the genetics of hearing loss in India are largely inadequate to facilitate genetic testing for carrier screening or prenatal diagnosis.
In an attempt to estimate the prevalence of GJB2 mutations in Indian population, we recruited 220 individuals with congenital, bilateral, severe-profound, sensorineural non-syndromic hearing loss and family history consistent with DFNB and sequenced the GJB2 gene. Contrary to the scenario worldwide, homozygous or compound heterozygous GJB2 mutations contributed for only 19% (42/220) of DFNB. Heterozygous GJB2 mutations were detected in 21% (47/220). The common mutations included W24X, R127H, W77X while M1V, V27I, 35insG were only occasionally found. Analysis of the parents confirmed their carrier status and also provided an opportunity for prenatal diagnosis in future pregnancy.
The significant proportion of heterozygous GJB2 mutations in affected individuals indicates various possibilities including compound heterozygosity with another variation in the regulatory or non-coding region of GJB2 or a digenic inheritance. There is a need to discover other major players causing DFNB in India for offering genetic screening. Currently, we are analyzing GJB6 gene both for the common 342 kb deletion or other mutations and plan to perform linkage analysis for all the known loci for DFNB. The results of our ongoing study will be discussed in the current paper.