Abnormal lysosomal and ubiquitin‐proteasome pathways in 19p13.3 distal myopathy

• DOI: 10.1002/ana.20158
• Publication Date: 2004-06-28T17:06:34Z
• Authors: Claudia Di Blasi; Behzad Moghadaszadeh; Claudia Ciano; Tiziana Negri; Alessio Giavazzi; Ferdinando Cornelio; Lucia Morandi; Marina Mora
• Keywords: Adult; 0301 basic medicine; Proteasome Endopeptidase Complex; Genetic Linkage; Ubiquitin; Chromosome Mapping; Muscle Proteins; Middle Aged; Muscular Dystrophies; Pedigree; Cysteine Endopeptidases; 03 medical and health sciences; Multienzyme Complexes; Vacuoles; Humans; Lysosomes; Muscle, Skeletal; Chromosomes, Human, Pair 19; Biomarkers

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 immunochemical features the vacuoles, present in many fibers, indicate protein degradation abnormalities dysregulation lysosomal pathway activation ubiquitin‐proteasomal pathway. Linkage analysis localized defect to 19p13.3 locus region known genes. speculate that primary may be an abnormality or related components. Ann Neurol 2004;56:133–138