title: Neutral lipid-storage disease with myopathy and extended phenotype with novel PNPLA2 mutation.
abstract: BACKGROUND
  Neutral lipid-storage disease with myopathy is caused by mutations in PNPLA2, which produce skeletal and cardiac myopathy. We report a man with multiorgan neutral lipid storage and unusual multisystem clinical involvement, including cognitive impairment.
  
  
  METHODS
  Quantitative brain MRI with voxel-based morphometry and extended neuropsychological assessment were performed. In parallel, the coding sequences and intron/exon boundaries of the PNPLA2 gene were screened by direct sequencing.
  
  
  RESULTS
  Neuropsychological assessment revealed global cognitive impairment, and brain MRI showed reduced gray matter volume in the temporal lobes. Molecular characterization revealed a novel homozygous mutation in exon 5 of PNPLA2 (c.714C>A), resulting in a premature stop codon (p.Cys238*).
  
  
  CONCLUSIONS
  Some PNPLA2 mutations, such as the one described here, may present with an extended phenotype, including brain involvement. In these cases, complete neuropsychological testing, combined with quantitative brain MRI, may help to characterize and quantify cognitive impairment.
authors.affiliation: Department of Systems Medicine (Neurology), University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Massa
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Pozzessere
authors.affiliation: Department of Systems Medicine (Neurology), University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Rastelli
authors.affiliation: Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Serra
authors.affiliation: Department of Systems Medicine (Neurology), University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Terracciano
authors.affiliation: Department of Systems Medicine (Neurology), University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Gibellini
authors.affiliation: Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bozzali
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Arca
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D008297:Male; D009135:Muscular Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D000217:Acyltransferases
chemical_list: D008049:Lipase; C494794:PNPLA2 protein, human; D000217:Acyltransferases
keywords: PNPLA2 mutation; brain; cognitive impairment; myopathy; neutral lipid-storage disease