Severe hypertriglyceridemia (HTG) is a relatively common form of dyslipidemia with a complex pathophysiology and serious health complications. HTG can develop in the presence of rare genetic factors disrupting genes involved in the triglyceride (TG) metabolic pathway, including large-scale copy-number variants (CNVs). Improvements in next-generation sequencing technologies and bioinformatic analyses have better allowed assessment of CNVs as possible causes of or contributors to severe HTG. We screened targeted sequencing data of 632 patients with severe HTG and identified partial deletions of the LPL gene, encoding the central enzyme involved in the metabolism of TG-rich lipoproteins, in four individuals (0.63%). We confirmed the genomic breakpoints in each patient with Sanger sequencing. Three patients carried an identical heterozygous deletion spanning the 5' untranslated region (UTR) to LPL exon 2, and one patient carried a heterozygous deletion spanning the 5'UTR to LPL exon 1. All four heterozygous CNV carriers were determined to have multifactorial severe HTG. The predicted null nature of our identified LPL deletions may contribute to relatively higher TG levels and a more severe clinical phenotype than other forms of genetic variation associated with the disease, particularly in the polygenic state. The identification of novel CNVs in patients with severe HTG suggests that methods for CNV detection should be included in the diagnostic workup and molecular genetic evaluation of patients with high TG levels.

中文翻译：

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LPL部分缺失：罕见的拷贝数变异导致严重的高甘油三酯血症。

严重的高甘油三酸酯血症（HTG）是血脂异常的一种相对常见的形式，具有复杂的病理生理学和严重的健康并发症。HTG可以在存在罕见的遗传因子破坏涉及甘油三酸酯（TG）代谢途径的基因（包括大规模拷贝数变异体（CNV））的情况下发展。下一代测序技术和生物信息学分析的改进更好地允许对CNV进行评估，将其作为严重HTG的可能原因或成因。我们筛选了632例重度HTG患者的靶向测序数据，并鉴定了LPL的部分缺失基因，编码参与富含TG的脂蛋白代谢的中心酶的基因，有四个个体（0.63％）。我们通过Sanger测序证实了每位患者的基因组断点。三名患者携带相同的杂合子，横跨LPL外显子2的5'非翻译区（UTR），一名患者携带杂合子的缺失，横跨LPL外显子1的5'UTR 。 。我们确定的LPL的预测无效性质与疾病相关的其他形式的遗传变异，尤其是在多基因状态下，缺失可能导致相对较高的TG水平和更严重的临床表型。重度HTG患者中新型CNV的鉴定表明，应将CNV检测方法包括在高TG水平患者的诊断检查和分子遗传学评估中。