Molecular Dissection of hypoapoC-II caused by defective mRNA transcription

家族性载脂蛋白C-II(apoC-II)缺乏症是一种罕见的常染色体隐性遗传病，其显著的高甘油三酯血症是由于LPL激活受损引起的。在大多数apoC-II缺乏症患者中，apoC-II基因的蛋白编码区存在致病突变；然而，一些非典型的apoC-II缺乏症患者的血浆apoC-II蛋白水平显著降低(以下称为低apoC-II)。发现一例apoC-II缺乏症，其表型与低apoC-II相同。我们利用单核/巨噬细胞培养系统证明了患者细胞中apoC-II mRNA的转录减少。然而，在患者的APOC2基因中检测到的所有50个单核苷酸变异都是常见的变异，推测这些变异不是导致的，这意味着其他突变调节apoC-II水平。全基因组测序正在进行中，以确定致病突变。

Familial apolipoprotein C-II (apoC-II) deficiency is a rare autosomal recessive disorder with marked hypertriglyceridemia resulting from impaired activation of LPL. In most cases of apoC-II deficiency, causative mutations have been found in the protein-coding region of APOC2 gene; however, several atypical cases of apoC-II deficiency were reported to have markedly reduced, but detectable levels of plasma apoC-II protein (hereafter referred to as hypoapoC-II). A case of apoC-II deficiency was found that is phenotypically identical to hypoapoC-II. We took advantage of a monocyte/macrophage culture system to prove that transcription of apoC-II mRNA was decreased in the patient's cells. However, all of the fifty single nucleotide variants detected in the patient's APOC2 gene were common variants that are supposedly not causative, implying that other mutations regulate apoC-II levels. Whole-genome sequencing is underway to identify the causative mutation.