PMID- 10477434
OWN - NLM
STAT- MEDLINE
DCOM- 19991012
LR  - 20171116
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 14
IP  - 3
DP  - 1999
TI  - Molecular basis of late-life globoid cell leukodystrophy.
PG  - 256-62
AB  - Globoid cell leukodystrophy is an autosomal recessive inherited disease caused by
      deficiency of the lysosomal enzyme galactocerebrosidase (GALC). Although the
      severe, rapidly progressing infantile form is the most common, late-onset forms
      have been described. We investigated the molecular basis of GALC deficiency in a 
      patient with a late-life mild form of globoid cell leukodystrophy who survived
      into the eighth decade. Since material suitable for mutation analysis was no
      longer available from the proband, her GALC genotype was reconstructed by
      analyzing this gene in her six obligate carrier offspring. One allele contained
      the mutation 809G>A (G270D) in the 1637C background, while the other allele
      contained three sequence variants: 1609G>A (G537R), 1873G>A (A625T), and 1650T>A 
      (V550V) in the 1637T background. These mutations were confirmed in the proband's 
      genomic DNA isolated from a sural nerve biopsy. Expression studies indicated that
      the G537R is a disease-causing mutation, as it resulted in no GALC activity,
      either alone or together with the A625T. This A625T sequence variant did not
      affect the enzyme activity, at least when expressed in the 1637T background. The 
      mild clinical phenotype was likely to be associated with the 809G>A, since
      residual GALC activity, about 17% of the control activity, was detected in the
      expression studies of this mutation. This mutation has been found in several
      other patients with late-onset GLD.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - De Gasperi, R
AU  - De Gasperi R
AD  - Department of Neurology, New York University School of Medicine, New York, New
      York 10016, USA. desgar01@med.nyu.edu
FAU - Gama Sosa, M A
AU  - Gama Sosa MA
FAU - Sartorato, E
AU  - Sartorato E
FAU - Battistini, S
AU  - Battistini S
FAU - Raghavan, S
AU  - Raghavan S
FAU - Kolodny, E H
AU  - Kolodny EH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (DNA, Complementary)
RN  - EC 3.2.1.46 (Galactosylceramidase)
SB  - IM
MH  - Age of Onset
MH  - Aged
MH  - Alleles
MH  - Animals
MH  - COS Cells
MH  - DNA Mutational Analysis
MH  - DNA, Complementary/genetics
MH  - Exons/genetics
MH  - Female
MH  - Galactosylceramidase/*genetics
MH  - Gene Expression
MH  - Genetic Carrier Screening
MH  - Genotype
MH  - Humans
MH  - Leukodystrophy, Globoid Cell/*enzymology/genetics
MH  - Lymphocytes
MH  - Pedigree
MH  - Point Mutation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sural Nerve/metabolism
MH  - Transfection
EDAT- 1999/09/08 00:00
MHDA- 1999/09/08 00:01
CRDT- 1999/09/08 00:00
PHST- 1999/09/08 00:00 [pubmed]
PHST- 1999/09/08 00:01 [medline]
PHST- 1999/09/08 00:00 [entrez]
AID - 10.1002/(SICI)1098-1004(1999)14:3<256::AID-HUMU9>3.0.CO;2-6 [pii]
AID - 10.1002/(SICI)1098-1004(1999)14:3<256::AID-HUMU9>3.0.CO;2-6 [doi]
PST - ppublish
SO  - Hum Mutat. 1999;14(3):256-62. doi:
      10.1002/(SICI)1098-1004(1999)14:3<256::AID-HUMU9>3.0.CO;2-6.