Publication Date:
1997-09-20
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sleat, D E -- Donnelly, R J -- Lackland, H -- Liu, C G -- Sohar, I -- Pullarkat, R K -- Lobel, P -- DK45992/DK/NIDDK NIH HHS/ -- NS30147/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1997 Sep 19;277(5333):1802-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9295267" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Aminopeptidases
;
Chromosome Mapping
;
Chromosomes, Human, Pair 11
;
Codon
;
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
;
Endopeptidases
;
Female
;
Glycosylation
;
Humans
;
Isoelectric Point
;
Lysosomes/*enzymology
;
Male
;
Mannosephosphates/analysis
;
Molecular Sequence Data
;
Molecular Weight
;
*Mutation
;
Neuronal Ceroid-Lipofuscinoses/enzymology/*genetics
;
Pepstatins/pharmacology
;
Peptide Hydrolases/*chemistry/deficiency/*genetics
;
Polymerase Chain Reaction
;
Serine Proteases
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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