背景:家族性乳糜微粒血症综合征(FCS)是一种罕见的单基因形式的严重高甘油三酯血症,由参与甘油三酯代谢的基因突变引起。在这里,我们报道了一例韩国家族性乳糜微粒血症综合征,该综合征是由糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(GPIHBP1)复合杂合缺失引起的.
方法:一名4岁男孩在4个月前偶然发现的严重高甘油三酯血症(3734mg/dL)进行评估。他的哥哥在9岁时也表现出2133mg/dL的甘油三酯水平升高。脂蛋白电泳显示乳糜微粒的存在,前β脂蛋白比例的增加,和低血清脂蛋白脂肪酶水平。患者的父母和第一哥哥的血脂状况稳定。对于可疑的FCS,使用基于下一代测序的31个脂质代谢相关基因分析进行基因检测,没有发现致病变异。然而,使用测序深度信息进行拷贝数变异筛选,提示存在包含GPIHBP1所有编码外显子的大量杂合缺失.进行实时定量聚合酶链反应以验证缺失位点。结果表明,兄弟姐妹有两个杂合拷贝数变异,由全基因和外显子4缺失组成,每个人都继承自父母。在17个月的随访期间,病人没有发展为胰腺炎,饮食干预后。
结论:这些由罕见的GPIHBP1缺失引起的家族性乳糜微粒血症的兄弟姐妹病例突出了拷贝数变异的实施-超越下一代测序-作为诊断的重要考虑因素。准确的基因诊断对于建立严重的高甘油三酯血症的病因是必要的。这增加了胰腺炎的风险。
BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare monogenic form of severe hypertriglyceridemia, caused by mutations in genes involved in triglyceride metabolism. Herein, we report the
case of a Korean family with familial chylomicronemia syndrome caused by compound heterozygous deletions of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1).
METHODS: A 4-year-old boy was referred for the evaluation of severe hypertriglyceridemia (3734 mg/dL) that was incidentally detected 4 months prior. His elder brother also demonstrated an elevated triglyceride level of 2133 mg/dL at the age of 9. Lipoprotein electrophoresis revealed the presence of chylomicrons, an increase in the proportion of pre-beta lipoproteins, and low serum lipoprotein lipase levels. The patient\'s parents and first elder brother had stable lipid profiles. For suspected FCS, genetic testing was performed using the next-generation sequencing-based analysis of 31 lipid metabolism-associated genes, which revealed no pathogenic variants. However, copy number variant screening using sequencing depth information suggested large heterozygous deletion encompassing all the coding exons of GPIHBP1. A real-time quantitative polymerase chain reaction was performed to validate the deletion site. The results showed that the siblings had two heterozygous copy number variants consisting of the whole gene and an exon 4 deletion, each inherited from their parents. During the follow-up period of 17 months, the patient did not develop pancreatitis, following dietary intervention.
CONCLUSIONS: These siblings\'
case of familial chylomicronemia syndrome caused by rare GPIHBP1 deletions highlight the implementation of copy number variants-beyond next-generation sequencing-as an important consideration in diagnosis. Accurate genetic diagnosis is necessary to establish the etiology of severe hypertriglyceridemia, which increases the risk of pancreatitis.