The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy.
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).
Fischer
Judith
J
Centre National de Génotypage, 91057 Evry Cedex, France. fischer@cng.fr
Lefèvre
Caroline
C
Morava
Eva
E
Mussini
Jean-Marie
JM
Laforêt
Pascal
P
Negre-Salvayre
Anne
A
Lathrop
Mark
M
Salvayre
Robert
R
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
D008049:Lipase; D010741:Phospholipases A; C494794:PNPLA2 protein, human; D000217:Acyltransferases