Case Series On Famlial Hypercholesterolemia

Abstract

The most common form of inherited lipid disorders is familial hypercholesterolemia (FH). It is characterized primarily by high concentrations of the clinical trial of low-density lipoprotein cholesterol, xanthomas (lipid deposits), xanthelasmata, arcus cornealis, and premature cardiovascular disease (CVD). We sought to identify new candidate genes responsible for the Cutaneous Xanthoma phenotype related with Familial Hypercholesterolemia by focusing on Vietnameses who met Dutch Lipid Clinic Network (DLCN) Criteria in the Diagnosis of FH. Autosomal dominant mutations in the following genes account for most cases of familial hypercholesterolaemia: LDLR (encoding the LDL receptor), APOB (encoding apolipoprotein B100 (apo B100), the LDLR ligand on the LDL particle) and PCSK9 (encoding proprotein convertase subtilisin/kexin type 9). The aim of the conducted study was to identify disease-causing mutations in FH-related and candidate genes in Vietnamese patients using next generation sequencing (NGS). Recruitment was performed using DLCN criteria. Targeted next generation sequencing was performed on a MiniSeq sequencer (Illumina, San Diego, CA, USA) using a 2x150 bp paired-end read module. Sequencing data analysis revealed pathogenic and possibly pathogenic variants in Cardio sequencing panel . The affected gene was LDLR. Two novel possibly pathogenic 2bp frameshift deletion c.1793_1794del in the exon 12 and 4bp frameshift insertion c.2197_2198insTATA in the exon 15 of the LDLR gene were found. Our findings are the first to identify the c.1793_1794del and c.2197_2198insTATA mutations in the LDLR gene. In addition, one published variant which was c.1867A >G in the exon 13 was also detected. The custom NGS panel proved to be an effective research tool for identifying new causative aberrations in a genetically heterogeneous disease as familial hypercholesterolemia (FH). Our findings expand the spectrum of variants associated with the FH loci and will be of value in genetic counseling among patients with the disease.