title: A myopathy with unusual features caused by PNPLA2 gene mutations.
abstract: BACKGROUND
  The PNPLA2 gene encodes the enzyme adipose triglyceride lipase (ATGL), which catalyzes the first step of triglyceride hydrolysis. Mutations in this gene are associated with an autosomal recessive lipid-storage myopathy, neutral lipid-storage disease with myopathy (NLSD-M).
  
  
  RESULTS
  A 72-year-old woman had late-onset myopathy, with mild weakness, cramps, and exercise intolerance. Electromyography showed myotonic discharges. A few leukocytes showed lipid droplets (Jordan anomaly). Deltoid and quadriceps muscle biopsies showed no lipid storage. Genetic analysis of PNPLA2 detected 2 heterozygous mutations: c.497A>G (p.Asp166Gly) in exon 5 and c.1442C>T (p.Pro481Leu) in exon 10. Expression of mutant PNPLA2 plasmids in HeLa cells resulted in impaired enzyme activity, confirming the pathological effects of the mutations.
  
  
  CONCLUSIONS
  In this case of NLSD-M, the myopathy may be due to a metabolic defect rather than to a mechanical effect of lipid storage. This suggests that more than 1 mechanism contributes to muscle damage in NLSD-M.
authors.affiliation: Division of Neurology, San Filippo Neri Hospital, Rome, Italy.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Pennisi
authors.forename: Sara
authors.initials: S
authors.lastname: Missaglia
authors.forename: Salvatore
authors.initials: S
authors.lastname: Dimauro
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bernardi
authors.forename: Hasan Orhan
authors.initials: HO
authors.lastname: Akman
authors.forename: Daniela
authors.initials: D
authors.lastname: Tavian
mesh_terms: D000368:Aged; D001706:Biopsy; D005260:Female; D006579:Heterozygote; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology*; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics*; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D000217:Acyltransferases
chemical_list: D008049:Lipase; C494794:PNPLA2 protein, human; D000217:Acyltransferases
keywords: ATGL enzyme; PNPLA2 gene; lipid metabolism; lipid myopathy; lipid storage