Three variants were identified in PPMS patients: KIF5A (associated with spastic paraplegia 10), MLC1 (associated with megalencephalic leukodystrophy with subcortical cysts), and REEP1 (associated with spastic paraplegia 31), and the burden of genetic variants associated with HSP was higher in PPMS patients than controls. The gene discussed is REEP1; the disease is primary progressive multiple sclerosis.