title: A somatic cell defect is associated with the onset of neurological symptoms in a lysosomal storage disease.
abstract: Mutations in individuals with the lysosomal storage disorder Niemann-Pick disease, type C1 (NPC1) are heterogeneous, not localized to specific protein domains, and not correlated to time of onset or disease severity. We demonstrate direct correlation of the time of neurological symptom onset with the severity of lysosomal defects in NPC1 patient-derived fibroblasts. This is a novel assay for NPC1 individuals that may be predictive of NPC1 disease progression and broadly applicable to other lysosomal disorders.
authors.affiliation: Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Rodriguez-Gil
authors.forename: Denise M
authors.initials: DM
authors.lastname: Larson
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Wassif
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Yanjanin
authors.forename: Stacie M
authors.initials: SM
authors.lastname: Anderson
authors.forename: Martha R
authors.initials: MR
authors.lastname: Kirby
authors.forename: Niraj S
authors.initials: NS
authors.lastname: Trivedi
authors.forename: Forbes D
authors.initials: FD
authors.lastname: Porter
authors.forename: William J
authors.initials: WJ
authors.lastname: Pavan
mesh_terms: D000293:Adolescent; D000328:Adult; D001692:Biological Transport / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016464:Lysosomal Storage Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology; D052556:Niemann-Pick Disease, Type C / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017434:Protein Structure, Tertiary
chemical_list: D008562:Membrane Glycoproteins
keywords: Lysosomal storage disorders; NPC1; Neurodegenerative disorders; Niemann–Pick disease, type C1