MUTATIONS IN THE PROTEOLIPID PROTEIN GENE IN JAPANESE FAMILIES WITH PELIZAEUS-MERZBACHER DISEASE

Pelizaeus-Merzbacher disease (PMD) is a rare X-Linked dysmyelinating d isorder of the CNS resulting from abnormalities in the proteolipid pro tein (PLP) gene. Exonic mutations in the PLP gene are present in 10 to 25% of all cases. In investigating genotype-phenotype correlations, w e screened five Japanese families with PMD for PLP gene mutations and compared their clinical manifestations. We identified two novel nucleo tide substitutions in exon 5, at V208N and at P210L, in two families. In the remaining three families, there were no mutations detected. Alt hough all patients satisfied the criteria for the classical form of PM D, two families not carrying the mutations showed milder clinical mani festations than those with the mutations. Since linkage analysis has s hown homogeneity at the PLP locus in patients with PMD, our findings s uggest that there may be genetic abnormalities other than exonic mutat ions that cause milder forms of PMD.