DFNB1, the first locus to have been associated with deafness, has two major genes GJB2 & GJB6, whose mutations have played vital role in hearing impairment across many ethnicities in the world. In our present study we have focused on the role of these mutations in assortative mating hearing impaired families from south India. One hundred and six assortatively mating hearing impaired (HI) families of south Indian origin comprising of two subsets: 60 deaf marrying deaf (DXD) families and 46 deaf marrying normal hearing (DXN) families were recruited for this study. In the 60 DXD families, 335 members comprising of 118 HI mates, 63 other HI members and 154 normal hearing members and in the 46 DXN families, 281 members comprising of 46 HI and their 43 normal hearing partners, 50 other HI members and 142 normal hearing family members, participated in the molecular study. One hundred and sixty five (165) healthy normal hearing volunteers were recruited as controls for this study. All the participating members were screened for variants in GJB2 and GJB6 genes and the outcome of gene mutations were compared in the subsequent generation in begetting deaf offspring. The DFNB1 allele frequencies for DXD mates and their offspring were 36.98 and 38.67%, respectively and for the DXN mates and their offspring were 22.84 and 24.38%, respectively. There was a 4.6% increase in the subsequent generation in the DXD families, while a 6.75% increase in the DXN families, which demonstrates the role of assortative mating along with consanguinity in the increase of DFNB1 mutations in consecutive generations. Four novel variants, p.E42D (in GJB2 gene), p.Q57R, p.E101Q, p.R104H (in GJB6 gene) were also identified in this study. This is the first study from an Indian subcontinent reporting novel variants in the coding region of GJB6 gene. This is perhaps the first study in the world to test real-time, the hypothesis proposed by Nance et al. in 2000 (intense phenotypic assortative mating mechanism can double the frequency of the commonest forms of recessive deafness [DFNB1]) in assortative mating HI parental generation and their offspring.

Stuttering is a childhood‐onset fluency disorder, intertwined with physiological, emotional, and anxiety factors. The present study was designed to evaluate the recurrence of the reported mutations among three previously implicated (GNPTAB, GNPTG, NAGPA) candidate genes, in persons with stuttering from south India. Mutation screening was performed among 64 probands on 12 specific exons, by Sanger sequencing. A total of 12 variants were identified, which included five nonsynonymous, five synonymous, and two noncoding variants. Three unrelated probands harbored heterozygous missense variants at conserved coding positions across species (p. Glu1200Lys in GNPTAB, p. Ile268Leu in GNPTG and p. Arg44Pro in NAGPA). Of these, only one variant (p. Glu1200Lys in GNPTAB) cosegregated with the affected status while p. Ile268Leu in GNPTG gene was found to be a rare de novo variant. Although this study identified some previously reported variants that have been claimed to have a role in stuttering, we confirmed only one of these to be a likely causal de novo variant (p.Ile268Leu) in the GNPTG gene at an allele frequency of 0.8% (1/128) in the families with stuttering.