Does Primary Progressive MS Share Pathogenic Genes with Other Degenerative Disorders?

Investigators sought to determine whether patients with primary progressive multiple sclerosis (PPMS) were enriched for mutations in genes associated with hereditary spastic paraplegia. Whole genome sequencing began in a discovery cohort of 38 PPMS patients and 81 controls matched for European ancestry. Replication cohorts included 746 PPMS, 3049 relapsing-remitting (RR) MS, and 1000 healthy controls.

The investigators identified four phenocopy variants in the discovery cohort with PPMS that were also observed in higher frequency in PPMS patients in the replication cohorts. These variants included mutations in KIF5A, a dominant variant for spastic paraplegia; MLC1, a recessive variant for megalencephalic leukodystrophy with subcortical cysts…