Homozygous missense mutation (G56R) in glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1) in two siblings with fasting chylomicronemia (MIM 144650).
Homozygous missense mutation (G56R) in glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1) in two siblings with fasting chylomicronemia (MIM 144650).
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DOI：
10.1186/1476-511x-6-23
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发表时间：
2007-09-20
影响因子：
4.5
通讯作者：
Hegele RA
中科院分区：
文献类型：
--
作者：
Wang J;Hegele RA
编码糖基磷脂酰肌醇锚定的高密度脂蛋白结合蛋白 1 (GPI-HBP1) 的 Gpihbp1 基因缺失的小鼠会出现严重的乳糜微粒血症。我们从 160 名患有空腹乳糜微粒血症且血浆甘油三酯 >10 mmol/L 的无关成年人的基因组 DNA 中筛选了人类同源物 – GPIHBP1 的编码区，每个人的 LPL 和 APOC2 基因序列均正常。一名患有严重 5 型高脂蛋白血症 (MIM 144650)、空腹乳糜微粒血症和对标准治疗耐药的复发性胰腺炎的患者被发现是一种新型 GPIHBP1 错义变异（即 G56R）的纯合子。 600 名对照受试者和 610 名高脂血症患者的基因组中不存在这种突变。 GPIHBP1 G56 残基在整个进化过程中一直保守，预计 G56R 突变会损害功能。她的纯合兄弟还患有难治性乳糜微粒血症和复发性胰腺炎以及早期冠心病。家系中G56R杂合子患有轻度空腹高甘油三酯血症。因此，一种非常罕见的 GPIHBP1 错义突变似乎与严重的高甘油三酯血症和乳糜微粒血症有关。
Mice with a deleted Gpihbp1 gene encoding glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1) develop severe chylomicronemia. We screened the coding regions of the human homologue – GPIHBP1 – from the genomic DNA of 160 unrelated adults with fasting chylomicronemia and plasma triglycerides >10 mmol/L, each of whom had normal sequence of the LPL and APOC2 genes. One patient with severe type 5 hyperlipoproteinemia (MIM 144650), fasting chylomicronemia and relapsing pancreatitis resistant to standard therapy was found to be homozygous for a novel GPIHBP1 missense variant, namely G56R. This mutation was absent from the genomes of 600 control subjects and 610 patients with hyperlipidemia. The GPIHBP1 G56 residue has been conserved throughout evolution and the G56R mutation was predicted to have compromised function. Her homozygous brother also had refractory chylomicronemia and relapsing pancreatitis together with early coronary heart disease. G56R heterozygotes in the family had fasting mild hypertriglyceridemia. Thus, a very rare GPIHBP1 missense mutation appears to be associated with severe hypertriglyceridemia and chylomicronemia.