Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, CHANARIN-DORFMAN-SYNDROME, FAMILY-MEMBERS, LIPOLYSIS, METABOLISM, EXPRESSION, PROTEIN, CGI-58, Cells, Cultured, DNA Mutational Analysis, Female, Humans, Lipase, Lipidoses, Muscular Diseases, Mutation, Phospholipases A, RNA Interference, Transfection, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 3001 Agricultural biotechnology, 3102 Bioinformatics and computational biology, 3105 Genetics

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).