Abstract
Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease whose defective gene has remained elusive. A molecular basis for LINCL was determined with an approach applicable to other lysosomal storage diseases. When the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, a single protein was identified that is absent in LINCL. Sequence comparisons suggest that this protein is a pepstatin-insensitive lysosomal peptidase, and a corresponding enzymatic activity was deficient in LINCL autopsy specimens. Mutations in the gene encoding this protein were identified in LINCL patients but not in normal controls.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Aminopeptidases
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Chromosome Mapping
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Chromosomes, Human, Pair 11
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Codon
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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Endopeptidases
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Female
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Glycosylation
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Humans
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Isoelectric Point
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Lysosomes / enzymology*
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Male
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Mannosephosphates / analysis
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Molecular Sequence Data
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Molecular Weight
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Mutation*
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Neuronal Ceroid-Lipofuscinoses / enzymology
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Neuronal Ceroid-Lipofuscinoses / genetics*
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Pepstatins / pharmacology
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Peptide Hydrolases / chemistry*
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Peptide Hydrolases / deficiency
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Peptide Hydrolases / genetics*
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Polymerase Chain Reaction
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Serine Proteases
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Tripeptidyl-Peptidase 1
Substances
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Codon
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Mannosephosphates
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Pepstatins
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Tripeptidyl-Peptidase 1
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Streptomyces pepsin inhibitor
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mannose-6-phosphate
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Endopeptidases
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Peptide Hydrolases
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Serine Proteases
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Aminopeptidases
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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pepstatin
Associated data
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GENBANK/AF017456
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GENBANK/AF039704