Severe Hyperlipidemia and Multifocal Atherosclerosis With Negative Genetic Testing for Familial Hypercholesterolemia: A Case Report

作者：Buczyński D, Róg A, Pałka M, Susuł M, Rajtar-Salwa R · 发表于：Cureus · 年份：2026 · DOI：10.7759/cureus.110527

Familial hypercholesterolemia (FH) is a genetic disorder characterized by severely elevated cholesterol levels and increased cardiovascular risk. While typically associated with mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes, many clinical cases remain genetically unexplained. Identifying novel variants in non-canonical genes is essential for understanding the complex genetic architecture of lipid disorders. A 75-year-old female patient presented with severe hyperlipidemia, multifocal atherosclerosis, and multiple comorbidities. Her native low-density lipoprotein cholesterol (LDL-C) was 6.7 mmol/L. Based on a Dutch Lipid Clinic Network (DLCN) score of 9 (5 points for LDL-C level, 2 points for personal premature coronary artery disease (CAD), and 2 points for a first-degree relative - specifically the patient's father - with xanthomata of the Achilles tendons area, with personal tendon xanthomata and corneal arcus being absent), a clinical diagnosis of definite familial hypercholesterolemia was established. Furthermore, an elevated lipoprotein(a) level of 407.5 nmol/L was identified as an independent cardiovascular risk factor. Comprehensive genetic testing revealed no pathogenic mutations in the LDLR, APOB, or PCSK9 genes. However, molecular analysis identified a heterozygous variant of uncertain significance (VUS), c.7031G>T p.(Arg2344Leu), in the Cadherin EGF LAG Seven-Pass G-...