Mutational genetic spectrum in isolated dystonia in a Spanish cohort and systematic review

Takeaway

  • There is a disparate genetic contribution to inherited isolated dystonia (IDT) regarding age at onset, site of dystonia onset and final distribution from DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype.

Why this matters

  • IDT, sustained/intermittent involuntary muscle contractions with no other neurological sign, has been linked to several genes, including TOR1A (encodes an adenosine triphosphatase), THAP1 (encodes DNA-binding transcription factor) and GNAL (encodes a GTP binding protein); however, their true impact on IDT is unknown.

  • Elucidation of the involvement of TOR1A, THAP1 and GNAL variants in IDT pathogenesis provides a starting point for further clinical research into both their potential role as IDT biomarkers, and for development of targeted therapies for these patients.