Genetic factors and therapy outcomes in persistent developmental stuttering.

Purpose: We investigated whether outcomes of therapy for persistent developmental stuttering differ in individuals who carry a mutation in one of the known genes associated with stuttering compared to individuals without such mutations.

Method: We studied outcomes of an intensive fluency shaping-based therapy program in individuals with persistent developmental stuttering. We evaluated a cohort of 51 stuttering individuals with who carried a mutation in either the GNPTAB, GNPTG, NAGPA, or AP4E1 gene.

Mucolipidosis types II and III and non-syndromic stuttering are associated with different variants in the same genes.

Homozygous mutations in GNPTAB and GNPTG are classically associated with mucolipidosis II (ML II) alpha/beta and mucolipidosis III (ML III) alpha/beta/gamma, which are rare lysosomal storage disorders characterized by multiple pathologies. Recently, variants in GNPTAB, GNPTG, and the functionally related NAGPA gene have been associated with non-syndromic persistent stuttering. In a worldwide sample of 1013 unrelated individuals with non-syndromic persistent stuttering we found 164 individuals who carried a rare non-synonymous coding variant in one of these three genes.