WGS and replication studies identified three pathogenic variants in PPMS patients that cause neurological disorders sharing features with MS: KIF5A p.Ala361Val in spastic paraplegia 10; MLC1p.Pro92Ser in megalencephalic leukodystrophy with subcortical cysts, and REEP1 c.606 + 43G>T in Spastic Paraplegia 31.
Mutations in the genes encoding the astrocytic protein MLC1, the cell adhesion molecule GlialCAM or the Cl(-) channel ClC-2 underlie human leukodystrophies.
This disorder is very similar to megalencephalic leukoencephalopathy with subcortical cysts (MLC), a newly characterized leukodystrophy whose molecular basis was recently shown to be mutations in a gene (KIAA0027) that has been renamed MLC1.