Evaluation of recurrent GNPTAB, GNPTG, and NAGPA variants associated with stuttering

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.