Recurrence of reported GNPTAB, GNPTG and NAGPA gene variations
associated with stuttering - an evaluation
Abstract
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 (PWS) from south India. Mutation screening was
performed on 64 probands on 12 specific exons, by Sanger sequencing. A
total of 12 variants were identified, which included five nonsynonymous
missense, five synonymous and two non coding variants. Only three
unrelated probands, harbored heterozygous likely pathogenic missense
variants (c.3598G>A in GNPTAB, c.802A>C in
GNPTG and c.131G>C in NAGPA) resulting in an overall
frequency of 4.7% and an allele frequency of 2.3% (3/128*100). Among
the three likely pathogenic variants only two co-segregated
(c.3598G>A in GNPTAB - STU 29 and c.802A>C in
GNPTG - STU 63) with the affected status reducing the likely pathogenic
allele frequency to 1.6% (2/128*100). The recurrence of pathogenic
variants in our study corroborate the causative role of these genes in
stuttering but still remains unknown as to how the speech dysfluency
occurs even in its heterozygous condition. Keywords: Stuttering,
candidate genes, GNPTAB, GNPTG, NAGPA