Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive neur
odegenerative disorder that affects both the central and peripheral nervous
system due to an enzymatic defect of galactocerebrosidase (GALC). Followin
g its cloning, many mutations in the galactocerebrosidase gene have been re
ported, but the correlation between phenotype and genotype was not clear in
many cases. In this study we further investigated the molecular defects in
another 10 patients (6 Japanese and 4 non-Japanese), using cultured skin f
ibroblasts, and found 10 mutations, of which 8 were novel, including a nons
ense mutation (W647X) and 7 missense mutations (G43R, S52F, T262I, Y319C, W
410G, R515H, T652R) in the coding region. Some phenotype-specific mutations
were found but the other mutations were private. Mutations reported so far
have been distributed over the whole GALC gene and it is difficult to spec
ulate on functional domains of the GALC protein and phenotypically specific
regions.