title: Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis.
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.
authors.affiliation: Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Sleat
authors.forename: R J
authors.initials: RJ
authors.lastname: Donnelly
authors.forename: H
authors.initials: H
authors.lastname: Lackland
authors.forename: C G
authors.initials: CG
authors.lastname: Liu
authors.forename: I
authors.initials: I
authors.lastname: Sohar
authors.forename: R K
authors.initials: RK
authors.lastname: Pullarkat
authors.forename: P
authors.initials: P
authors.lastname: Lobel
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003062:Codon; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D005260:Female; D006031:Glycosylation; D006801:Humans; D007526:Isoelectric Point; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D008360:Mannosephosphates / Q000032:analysis; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology / Q000235:genetics*; D010436:Pepstatins / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics*; D016133:Polymerase Chain Reaction; D057057:Serine Proteases; D000091346:Tripeptidyl-Peptidase 1
chemical_list: D003062:Codon; D008360:Mannosephosphates; D010436:Pepstatins; D000091346:Tripeptidyl-Peptidase 1; C014195:Streptomyces pepsin inhibitor; C027693:mannose-6-phosphate; D010450:Endopeptidases; D010447:Peptide Hydrolases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C031375:pepstatin