Variants in GNPTAB, GNPTG and NAGPA genes are associated with stutterers.

Abstract

Non-syndromic stuttering is a neurodevelopmental disorder characterized by disruptions in normal flow of speech in the form of repetition, prolongation and involuntary halts. Previously, mutations with more severe effects on GNPTAB and GNPTG have been reported to cause Mucolipidosisll (ML-ll) and Mucolipidosislll (ML-lll), two lysosomal storage disorders with multiple pathologies. We used homozygosity mapping and Sanger sequencing to investigate variants of the three genes in 25 Iranian families with at least two first degree related non-syndromic stutterers. Bioinformatic evaluation and Segregation analysis of the found variants helped us define probable consequences. We also compared our findings with those related to Mucolipidosis. 14 variations were found in the three genes 3 of which, including a novel variant within intronic region of GNPTG and a heterozygous 2-bp deletion in coding region of GNPTAB, co-segregated with stuttering in the families they were found. Bioinformatics analysis predicted all three variants causing deleterious effects on gene functioning. Our findings support the role of these three variants in non-syndromic stuttering. This finding may challenge the current belief that variations causing stuttering are at different sites and have less severe consequences than genetic changes that cause ML-ll and ML-lll.