Position effect at the SOX3 locus by an interchromosomal insertion causes hereditary spastic paraplegia

The Xq27.1 region is a hotspot for interchromosomal insertions associated with diverse phenotypes. We describe a family with X-linked inheritance of hereditary spastic paraplegia linked to an interchromosomal insertion. Functional investigations indicate that the disease mechanism is pathogenic rewiring of the three-dimensional genome architecture, resulting in transcriptional dysregulation of SOX3.