Novel mutations in the adipose triglyceride lipase gene causing neutral lipid storage disease with myopathy
Novel mutations in the adipose triglyceride lipase gene causing neutral lipid storage disease with myopathy
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DOI：
10.1016/j.bbrc.2008.10.081
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发表时间：
2008-12-19
影响因子：
3.1
通讯作者：
Arca, Marcello
中科院分区：
文献类型：
--
作者：
Campagna, Filomena;Nanni, Luisa;Arca, Marcello
中性脂质沉积病的一个亚组最近与肌病（NLSDM）相关，并归因于编码参与细胞内甘油三酯降解的脂肪甘油三酯脂肪酶的基因（PNPLA 2）突变。到目前为止，已经描述了5例NLSDM患者，我们报告了另外3例患者。一名44岁的伊朗妇女和两名意大利兄弟，年龄分别为40岁和35岁，表现为运动不耐受和近端肢体无力，CK水平升高和乔丹异常。肌肉活检显示所有患者均出现明显的中性脂质蓄积。对PNPLA 2基因的10个外显子和内含子-外显子连接进行测序。在PNPLA 2基因第5外显子发现两个新的纯合突变（c.695delT和c.542delAC）。两种突变均导致移码，导致提前终止密码子（分别为p.L255X和p.1212X）。这些突变预测了缺少C-末端疏水结构域的截短PNPLA 2蛋白。这些发现表明NLSDM是罕见的，但遗传异质性。(C)2008年爱思唯尔公司All rights reserved.
A subgroup of neutral lipid storage disease has been recently associated with myopathy (NLSDM) and attributed to mutations in the gene (PNPLA2) encoding an adipose triglyceride lipase involved in the degradation of intracellular triglycerides. Five NLSDM patients have been described thus far and we reported three additional patients. A 44-year old Iranian woman and two Italian brothers, aged 40 and 35, presented with exercise intolerance and proximal limb weakness, elevated CK levels, and Jordan's anomaly. Muscle biopsies showed marked neutral lipid accumulation in all patients. The 10 exons and the intron-exon junctions of the PNPLA2 gene were sequenced. Two novel homozygous mutations in exon 5 of PNPLA2 gene were found (c.695delT and c.542delAC). Both mutations resulted in frameshifts leading to premature stop codons (p.L255X and p.1212X, respectively). These Mutations predict a truncated PNPLA2 protein lacking the C-terminal hydrophobic domain. These findings indicate that NLSDM is rare, but genetically heterogeneous. (C) 2008 Elsevier Inc. All rights reserved.