The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy
The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy
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DOI：
10.1038/ng1951
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发表时间：
2007-01-01
期刊：
影响因子：
30.8
通讯作者：
Salvayre, Robert
中科院分区：
文献类型：
--
作者：
Fischer, Judith;Lefevre, Caroline;Salvayre, Robert
中性脂肪沉积病是一组常染色体隐性遗传病，其特征是甘油三酯在细胞质液滴中全身性积聚。在这里，我们报告了一个中性脂肪沉积疾病亚组，其特征是轻度肌病，没有鱼鳞病，脂肪甘油三酯脂肪酶(PNPLA2，也称为ATGL)的两个等位基因都发生了突变。其中三个突变被预测为导致ATGL蛋白被截断，其完整的Patatin结构域包含活性部位，但在疏水结构域中存在缺陷。针对ATGL的短干扰RNA模拟了甘油三酯降解的阻断。NLSDM不同于Chanarin-Dorfman综合征，Chanarin-Dorfman综合征的特征是中性脂肪堆积性疾病伴鱼鳞病、轻度肌病和由于ABHD5(也称为CGI-58)突变导致的肝肿大。
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).