We have recently analysed the original SPG family and mapped the gene to a region ofXq21. 3-q24 which includes the PLP locus (HK et al., manuscript submitted). Recently, a point mutation (His139Tyr) was found in exon 3B of PLP in an X-linked SPG family (SPG2) without optic atrophy. This mutation results in a mutant PLP protein, but a normal DM20 protein which is an alternatively spliced transcript from the PLP gene. These data showed that SPG2 and PMD are allelic disorders8• We have examined PLPin the original X-linked SPG family using SSCP and direct sequencing methods. We found a point mutation (T to C) in exon 4 of affected males which alters Ile to Thr at residue 186. This change was absent in the unaffected males of the family and in 40 unrelated control females (see Fig). Surprisingly, this mutation is identical to the mutation previously identified in the rumpshaker mouse model9• Rumpshakeris an allele of the jimpy locus10• Most jimpy alleles are clinically similar to PMD, and jimpy mice show failure of development and differentiation of oligodendrocytes leading to early death. Rumpshaker mice, although myelin-deficient like other jimpy mutants, have normal