Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia

Pseudonymized blood samples will undergo high-molecular-weight DNA extraction, followed by long-read whole-genome sequencing (lrWGS) using Oxford Nanopore technology. Index cases will be sequenced at high depth (\>30X), while relatives will be multiplexed (\>15X). Sequencing data will be analyzed through a dedicated bioinformatics pipeline to detect SNVs, indels, structural variants, and repeat expansions. Results will be interpreted by expert teams and discussed in monthly clinical-genetic meetings. Variants of interest will be validated by appropriate molecular techniques, and family segregation will be assessed when relevant.