PMID- 10234611
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20190831
IS  - 0141-8955 (Print)
IS  - 0141-8955 (Linking)
VI  - 22
IP  - 2
DP  - 1999 Apr
TI  - Molecular heterogeneity of Krabbe disease.
PG  - 155-62
AB  - Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive
      neurodegenerative disorder that affects both the central and peripheral nervous
      system due to an enzymatic defect of galactocerebrosidase (GALC). Following its
      cloning, many mutations in the galactocerebrosidase gene have been reported, 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 fibroblasts, and found 10
      mutations, of which 8 were novel, including a nonsense mutation (W647X) and 7
      missense mutations (G43R, S52F, T262I, Y319C. W410G, 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 speculate on functional domains of the GALC protein and
      phenotypically specific regions.
FAU - Fu, L
AU  - Fu L
AD  - Department of Pediatrics, Faculty of Medicine, Osaka University, Japan.
      koji@ped.med.osaka-u.ac.jp
FAU - Inui, K
AU  - Inui K
FAU - Nishigaki, T
AU  - Nishigaki T
FAU - Tatsumi, N
AU  - Tatsumi N
FAU - Tsukamoto, H
AU  - Tsukamoto H
FAU - Kokubu, C
AU  - Kokubu C
FAU - Muramatsu, T
AU  - Muramatsu T
FAU - Okada, S
AU  - Okada S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Inherit Metab Dis
JT  - Journal of inherited metabolic disease
JID - 7910918
RN  - 0 (DNA, Complementary)
RN  - EC 3.2.1.46 (Galactosylceramidase)
RN  - OF5P57N2ZX (Alanine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Alanine/genetics
MH  - Animals
MH  - Blotting, Northern
MH  - COS Cells
MH  - DNA, Complementary
MH  - Galactosylceramidase/*genetics
MH  - Gene Deletion
MH  - Genetic Heterogeneity
MH  - Glycine/genetics
MH  - Humans
MH  - Leukodystrophy, Globoid Cell/*enzymology/*genetics
MH  - Mutagenesis
MH  - Polymorphism, Genetic
EDAT- 1999/05/11 00:00
MHDA- 1999/05/11 00:01
CRDT- 1999/05/11 00:00
PHST- 1999/05/11 00:00 [pubmed]
PHST- 1999/05/11 00:01 [medline]
PHST- 1999/05/11 00:00 [entrez]
AID - 10.1023/a:1005449919660 [doi]
PST - ppublish
SO  - J Inherit Metab Dis. 1999 Apr;22(2):155-62. doi: 10.1023/a:1005449919660.