Perera Shehan D, Wang Jian, McIntyre Adam D, Hegele Robert A
Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 4288A-1151 Richmond Street North, London, ON N6A 5B7, Canada.
Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON N6A 5B7, Canada.
Genes (Basel). 2025 Jan 5;16(1):55. doi: 10.3390/genes16010055.
Biallelic rare pathogenic loss-of-function (LOF) variants in lipoprotein lipase () cause familial chylomicronemia syndrome (FCS). Heterozygosity for these same variants is associated with a highly variable plasma triglyceride (TG) phenotype ranging from normal to severe hypertriglyceridemia (HTG), with longitudinal variation in phenotype severity seen often in a given carrier. Here, we provide an updated overview of genetic variation in in the context of HTG, with a focus on disease-causing and/or disease-associated variants. We provide a curated list of 300 disease-causing variants discovered in , as well as an exon-by-exon breakdown of the gene and protein, highlighting the impact of variants and the various functional residues of domains of the LPL protein. We also provide a curated list of variants of unknown or uncertain significance, many of which may be upgraded to pathogenic/likely pathogenic classification should an additional case and/or segregation data be reported. Finally, we also review the association between benign/likely benign variants in , many of which are common polymorphisms, and the TG phenotype.
脂蛋白脂肪酶（LPL）的双等位基因罕见致病性功能丧失（LOF）变异导致家族性乳糜微粒血症综合征（FCS）。这些相同变异的杂合性与高度可变的血浆甘油三酯（TG）表型相关，范围从正常到严重高甘油三酯血症（HTG），在给定携带者中经常可见表型严重程度的纵向变化。在此，我们提供了在HTG背景下LPL基因变异的最新概述，重点关注致病和/或疾病相关变异。我们提供了在LPL中发现的300个致病变异的精选列表，以及LPL基因和蛋白质的逐个外显子分解，突出了变异的影响以及LPL蛋白结构域的各种功能残基。我们还提供了意义未知或不确定的变异的精选列表，如果报告了额外的病例和/或分离数据，其中许多变异可能会升级为致病/可能致病分类。最后，我们还回顾了LPL中良性/可能良性变异（其中许多是常见多态性）与TG表型之间的关联。
