The test analyses six genes commonly involved in Familial Hypercholesterolemia (FH) using next-generation sequencing technology. This includes the LDLR, APOB, PCSK9 and APOE genes associated with autosomal dominant Familial Hypercholesterolemia, the LDLRAP1 gene associated with Autosomal Recessive Hypercholesterolemia (ARH) and the LIPA gene associated with Lysosomal Acid Lipase Deficiency (LALD).
The promoter and coding regions of each gene, including exon-intron boundaries,are analysed, in addition to copy number variations (CNV’s), such as deletions/duplications in the LDLR gene. CNV’ss are confirmed by Multiplex Ligation-dependent Probe Amplification (MLPA), and other selected variants by Sanger sequencing. In addition, the test detects the presence or absence of 28 common genetic variants known as Single Nucleotide Polymorphisms (SNPs), related to Polygenic Hypercholesterolemia, cardiovascular risk, and pharmacogenetics.
By genotyping these carefully selected SNPs, information can be gained that is useful in clinical and therapeutic management of patients. If a germline pathogenic/likely pathogenic variant is identified by LIPID inCode® testing, this confirms a genetic diagnosis of Familial Hypercholesterolemia in the individual, and genetic testing for the presence of this variant only is available to in at-risk family members using Sanger sequencing technology and MLPA.
