Familial combined hyperlipidemia (FCHL) is a common genetic disorder characterized by increased fasted serum cholesterol, triglycerides, and apolipoprotein B‐100. Molecular genetic techniques such as next generation sequencing have been very successful methods for rare variants finding with a moderate‐to large effect. In this study, we characterized a large pedigree from MASHAD study in northeast Iran with coinheritance of FCHL and early‐onset coronary heart disease. In this family, we used whole‐exome sequencing and Sanger sequencing to determine the disease‐associated gene. We identified a novel variant in the LPL gene, leading to a substitution of an asparagine for aspartic acid at position 151. The D151N substitution cosegregated with these characters in all affected family members in the pedigree but it was absent in all unaffected members in this family. We speculated that the mutation D151N in LPL gene might be associated with FCHL and early‐onset coronary heart disease in this family. However, the substantial mechanism requires further investigation.

中文翻译：

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LPL基因的新型变异与家族性合并高脂血症有关。

家族性合并高脂血症（FCHL）是一种常见的遗传性疾病，其特征在于禁食的血清胆固醇，甘油三酸酯和载脂蛋白B-100升高。诸如下一代测序之类的分子遗传技术已经非常成功地发现了罕见的变体，并且具有中到大的效果。在这项研究中，我们以MASHAD研究在伊朗东北部的特征为特征，该特征与FCHL和早期发作的冠心病相一致。在这个家族中，我们使用了全外显子测序和Sanger测序来确定与疾病相关的基因。我们在LPL中发现了一个新的变体基因，导致天冬氨酸在151位被天冬氨酸取代。D151N取代在谱系中所有受影响的家庭成员中与这些字符共分离，但在该家族中所有未受影响的成员中均不存在。我们推测，该家族中LPL基因的D151N突变可能与FCHL和早发性冠心病有关。但是，这种实质性机制需要进一步研究。