Focal dystonia gene hunt gets a new entry point: DystoniaGeneNet flags familial MRI signatures, then three new genes
Isolated focal dystonia has fewer than five known causal genes, and small families with incomplete penetrance make linkage analysis hard. A 3D convolutional network, DystoniaGeneNet, judged familial status from T1-weighted brain MRI and correctly classified 18 of 21 independent familial cases (85.7%), then guided exome variant prioritization and segregation analysis in 214 individuals. Rare variants segregating with disease emerged in RAP1GAP, TNN and ITSN2, all converging on perisynaptic extracellular matrix–synapse signalling.