Determination of regulatory motifs and pathogenicity of intronic variants of GNPTAB, GNPTG, and NAGPA genes in individuals with stuttering

Abstract

Abstract Background Stuttering is a fluency disorder typically characterized by part-word repetitions, voiced or voiceless sound prolongations, and broken words. Evidence suggests that 1% of the world population stutters. Compelling evidence from past research suggests that stuttering is caused by non-synonymous coding sites. This study evaluates the intronic regions of GNPTAB, GNPTG, and NAGPA genes for possible pathogenicity of intronic variants from unrelated non-syndromic stutterers in a cohort of the south Indian population. Results High-throughput sequencing revealed 41 intronic variants. Computational tool Reg-SNP Intron identified three intronic variants rs11110995 A>G, rs11830792 A>G, and rs1001171 T>A of having a plausible pathogenic impact which was identified in 37.9%, 26.5%, and 59.4% of stutterers, respectively. RegulomeDB identified the regulatory motifs and susceptible loci of the intronic variants. Conclusions This study imparts the identification, association, and interpretation of pathogenicity and regulatory significance of the intronic variants in the context of the noncoding DNA elements. Future work is warranted to better understand the role of the intronic variants in a larger cohort of stutterers, and a cohort of fluent controls would be valuable.