A NOVEL INSERTIONAL MUTATION AT EXON-VII OF THE MYELIN PROTEOLIPID PROTEIN GENE IN PELIZAEUS-MERZBACHER DISEASE

Pelizaeus-Merzbacher disease (PMD) is an X-linked neurological disorde r characterized by dysmyelination in the central nervous system (CNS). Recently mutations of the myelin proteolipid protein (PLP) gene which encodes both PLP and its isoform, DM-20 generated by alternative spli cing, have been demonstrated in PMD patients. We analyzed the seven ex ons of the PLP gene of a Japanese boy affected with PMD by direct sequ encing and identified an insertion event in exon VII of the PLP gene. This mutation was also present in his carrier mother, but was absent i n ninety-five X chromosomes of normal Japanese. The frame-shift mutati on leads to the production of truncated PLP with altered carboxyl term inal amino acid sequences, resulting in considerable change of the str ucture of PLP and DM-20 necessary for functional purposes. This is the first report of a mutation in exon VII of the PLP gene associated wit h PMD.