title: Abnormal lysosomal and ubiquitin-proteasome pathways in 19p13.3 distal myopathy.
abstract: We describe a second large Italian kindred with autosomal dominant vacuolar myopathy characterized by variable severity, adult-onset weakness of distal limb muscles, and no cardiac involvement. At least 19 individuals over four generations are affected. Histopathological and immunochemical features of the vacuoles, present in many fibers, indicate protein degradation abnormalities with dysregulation of the lysosomal pathway and activation of the ubiquitin-proteasomal pathway. Linkage analysis localized the defect to the 19p13.3 locus in a region with no known genes. We speculate that the primary defect may be an abnormality in the lysosomal degradation pathway or related components.
authors.affiliation: Division of Neuromuscular Diseases, National Neurological Institute C. Besta, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Di Blasi
authors.forename: Behzad
authors.initials: B
authors.lastname: Moghadaszadeh
authors.forename: Claudia
authors.initials: C
authors.lastname: Ciano
authors.forename: Tiziana
authors.initials: T
authors.lastname: Negri
authors.forename: Alessio
authors.initials: A
authors.lastname: Giavazzi
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Cornelio
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.forename: Marina
authors.initials: M
authors.lastname: Mora
mesh_terms: D000328:Adult; D015415:Biomarkers; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D008040:Genetic Linkage; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010375:Pedigree; D046988:Proteasome Endopeptidase Complex; D025801:Ubiquitin / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism
chemical_list: D015415:Biomarkers; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex