Journal ArticleDOI
Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis
David E. Sleat,Robert J. Donnelly,Henry Lackland,Henry Lackland,Chang Gong Liu,Istvan Sohar,Istvan Sohar,Raju K. Pullarkat,Peter Lobel,Peter Lobel +9 more
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TLDR
In this paper, the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, and a single protein was identified that is absent in LINCL.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.read more
Citations
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Prevalence of lysosomal storage disorders.
TL;DR: There was no significant increase in the rate of either clinical diagnoses or prenatal diagnoses of lysosomal storage disorders during the study period, and as a group, they are relatively common and represent an important health problem in Australia.
Journal ArticleDOI
Identification of HE1 as the Second Gene of Niemann-Pick C Disease
Saule Naureckiene,David E. Sleat,David E. Sleat,Henry Lackland,Anthony H. Fensom,Marie T. Vanier,Robert Wattiaux,Michel Jadot,Peter Lobel,Peter Lobel +9 more
TL;DR: Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.
Journal ArticleDOI
The molecular basis of human retinal and vitreoretinal diseases.
TL;DR: A comprehensive picture of retinal and vitreoretinal disorders, caused by mutations in more than 165 genes is presented, including biological, clinical, genetic and molecular information.
Journal ArticleDOI
Molecular genetics of the Finnish disease heritage.
TL;DR: Identification of mutated genes has provided tools for detailed analyses of molecular pathogenesis in Finnish diseases, many of which reveal a distinct tissue specificity of clinical phenotype, often providing novel information on biological processes and metabolic pathways essential for normal development and function of human cells and tissues.
Journal ArticleDOI
Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA.
Stefan Worgall,Dolan Sondhi,Neil R. Hackett,Barry E. Kosofsky,Minal V. Kekatpure,Nurunisa Neyzi,Jonathan P. Dyke,Douglas Ballon,Linda Heier,Bruce M. Greenwald,Paul J. Christos,Madhu Mazumdar,Mark M. Souweidane,Michael G. Kaplitt,Ronald G. Crystal +14 more
TL;DR: Assessment of the primary outcome variable suggests a slowing of progression of LINCL in the treated children, and it is proposed that additional studies to assess the safety and efficacy of AAV-mediated gene therapy for LINCL are warranted.
References
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The Metabolic and Molecular Bases of Inherited Disease
TL;DR: In this paper, the authors present a list of disorders of MITOCHONDRIAL FUNCTION, including the following: DISORDERS OF MIOCHONDRIC FERTILITY XIX, XVI, XIX.
Journal ArticleDOI
Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis
Jouni Vesa,Hellsten E,Linda A. Verkruyse,Laura A. Camp,Juhani Rapola,Pirkko Santavuori,Sandra L. Hofmann,Leena Peltonen +7 more
TL;DR: The identification, by positional candidate methods, of defects in the palmitoyl-protein thioesterase gene in all 42 Finnish INCL patients and several non-Finnish patients is reported, which results in intracellular accumulation of the polypeptide and undetectable enzyme activity in the brain of patients.
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Mitochondrial ATP synthase subunit c storage in the ceroid-lipofuscinoses (Batten disease).
David Palmer,Ian M. Fearnley,John E. Walker,Nicholas A. Hall,Brian D. Lake,Leonhard S. Wolfe,Matti Haltia,Ryan Dennis Martinus,Robert D. Jolly +8 more
TL;DR: Findings suggest that ovine ceroid-lipofuscinosis is caused by a specific failure in the degradation of subunit c after its normal inclusion into mitochondria, and its consequent abnormal accumulation in lysosomes.
Journal ArticleDOI
Inhibitors of lysosomal enzymes: accumulation of lipofuscin-like dense bodies in the brain
TL;DR: Injections of leupeptin or chloroquine into the brains of young rats induced the formation of lysosome-associated granular aggregates which closely resembled the ceroid-lipofuscin that accumulates in certain disease states and during aging.
Journal ArticleDOI
Studies on the reaction of fluorescamine with primary amines
Silvano De Bernardo,Manfred Weigele,Voldemar Toome,Karin Manhart,Willy Leimgruber,Peter Böhlen,Stanley Stein,Sidney Udenfriend +7 more
TL;DR: Fluorescamine is a useful reagent for the fluorometric assay of primary amines and its influence on the fluorogenic reaction of representative amines, and on their fluorophoric derivatives has been investigated and the results are reported.