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Science 19 September 1997:
Vol. 277. no. 5333, pp. 1802 - 1805
DOI: 10.1126/science.277.5333.1802
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Reports

Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis

David E. Sleat, Robert J. Donnelly, Henry Lackland, Chang-Gong Liu, Istvan Sohar, Raju K. Pullarkat, Peter Lobel *

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.

D. E. Sleat, H. Lackland, C.-G. Liu, I. Sohar, P. Lobel, Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854, USA and Department of Pharmacology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, NJ 08854, USA.
R. J. Donnelly, Department of Lab Medicine and Pathology, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
R. K. Pullarkat, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
*   To whom correspondence should be addressed.

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