The genetic landscape of childhood-onset dystonia in a nationwide Turkish cohort: Clinical spectrum, molecular diagnostics, and therapeutic implications - PubMed
4 hours ago
- #Therapeutic implications
- #Childhood-onset dystonia
- #Genetic diagnostics
- The study analyzed 81 childhood-onset dystonia (COD) patients from 19 centers in Turkey, identifying 62 pathogenic/likely pathogenic variants across 26 genes.
- Common genetic causes included KMT2B (16%), GCH1 (11.1%), SLC2A1 (11.1%), GNAO1 (8.6%), TOR1A (8.6%), and GNAL (6.2%), with many rare and ultra-rare etiologies also reported.
- Primary diagnostic methods were whole-exome sequencing (49.4%), single-gene testing (25.9%), and targeted gene panels (23.5%), with variants including SNVs, deletions, duplications, and one trinucleotide repeat expansion.
- Gene Ontology analysis showed neurotransmission (22.2%), gene expression (20.9%), and signaling (17.3%) as the top functional categories affected in COD.
- Genetic diagnosis led to treatment changes (e.g., pharmacotherapy modification or deep brain stimulation) in 60.5% of patients, with targeted therapies being more effective than symptomatic treatments (p = 0.0118).
- The study underscores the genetic and phenotypic diversity of COD, highlighting how molecular diagnostics can guide personalized therapeutic strategies.