St. Vincent's University Hospital

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.

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.