The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy

Judith Fischer; Caroline Lefèvre; Eva Morava; Jean Marie Mussini; Pascal Lafor̂t; Anne Negre-Salvayre; Mark Lathrop; Robert Salvayre

doi:10.1038/ng1951

The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy

Judith Fischer, Caroline Lefèvre, Eva Morava, Jean Marie Mussini, Pascal Lafor̂t, Anne Negre-Salvayre, Mark Lathrop, Robert Salvayre

Medical Genetics

Research output: Contribution to journal › Article › peer-review

332 Scopus citations

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).

Original language	English (US)
Pages (from-to)	28-30
Number of pages	3
Journal	Nature Genetics
Volume	39
Issue number	1
DOIs	https://doi.org/10.1038/ng1951
State	Published - Jan 2007

ASJC Scopus subject areas

Genetics

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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).",

author = "Judith Fischer and Caroline Lef{\`e}vre and Eva Morava and Mussini, {Jean Marie} and Pascal Lafo{\^r}t and Anne Negre-Salvayre and Mark Lathrop and Robert Salvayre",

note = "Funding Information: We wish to thank the patients and family members for their participation in this study. We are grateful to S. Cure for help in writing this manuscript and to J.C. Thiers for microscopy assistance. This study was supported by the Centre National de G{\'e}notypage (CNG), the Association Franc¸aise contre les Myopathies (AFM), INSERM and University Paul Sabatier Toulouse-3.",

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AU - Lafor̂t, Pascal

AU - Negre-Salvayre, Anne

AU - Lathrop, Mark

AU - Salvayre, Robert

N1 - Funding Information: We wish to thank the patients and family members for their participation in this study. We are grateful to S. Cure for help in writing this manuscript and to J.C. Thiers for microscopy assistance. This study was supported by the Centre National de Génotypage (CNG), the Association Franc¸aise contre les Myopathies (AFM), INSERM and University Paul Sabatier Toulouse-3.

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AB - 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).

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The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy

Abstract

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