title: The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy.
abstract: Neutral lipid storage disease comprises a heterogeneous group of autosomal recessive disorders characterized by systemic accumulation of triglycerides in cytoplasmic droplets. Here we report a neutral lipid storage disease subgroup characterized by mild myopathy, absence of ichthyosis and mutations in both alleles of adipose triglyceride lipase (PNPLA2, also known as ATGL). Three of these mutations are predicted to lead to a truncated ATGL protein with an intact patatin domain containing the active site, but with defects in the hydrophobic domain. The block in triglyceride degradation was mimicked by short interfering RNA directed against ATGL. NLSDM is distinct from Chanarin-Dorfman syndrome, which is characterized by neutral lipid storage disease with ichthyosis, mild myopathy and hepatomegaly due to mutations in ABHD5 (also known as CGI-58).
authors.affiliation: Centre National de Génotypage, 91057 Evry Cedex, France. fischer@cng.fr
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
authors.forename: Caroline
authors.initials: C
authors.lastname: Lefèvre
authors.forename: Eva
authors.initials: E
authors.lastname: Morava
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Mussini
authors.forename: Pascal
authors.initials: P
authors.lastname: Laforêt
authors.forename: Anne
authors.initials: A
authors.lastname: Negre-Salvayre
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Robert
authors.initials: R
authors.lastname: Salvayre
mesh_terms: D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008049:Lipase; D008064:Lipidoses / Q000235:genetics*; D009135:Muscular Diseases / Q000235:genetics*; D009154:Mutation; D010741:Phospholipases A / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D014162:Transfection; D000217:Acyltransferases
chemical_list: D008049:Lipase; D010741:Phospholipases A; C494794:PNPLA2 protein, human; D000217:Acyltransferases