Molecular diagnosis methods in familial hypercholesterolemia

Özet

Familial hypercholesterolemia (FH) is considered the genetic cause of coronary heart disease and ischemic stroke. FH is mainly an autosomalcodominant pattern-based disorder and is primarily determined by point mutations within the low-density lipoprotein receptor, apolipoprotein B, and proprotein convertase subtilisin/kexin type 9 genes, causing increased low-density lipoprotein cholesterol levels in the serum ofuntreated individuals. The accumulation will eventually lead to atherosclerotic cardiovascular disease. Although clinical criteria comprising several prognosis scores, such as the Simon Broome, Dutch Lipid Clinic Network, Make Early Diagnosis to Prevent Early Death, andthe recently proposed Montreal-FH-SCORE, are the conventional basis of diagnosing FH, the genetic diagnosis made by single nucleotidepolymorphism genotyping, multiplex ligation-dependent probe amplification analysis, and sequencing (both Sanger and Next-Generation sequencing) offers unequivocal diagnosis. Given the heterogeneity of known mutations, the genetic diagnosis of FH is often difficult to establish,despite the growing evidence of the causative mutations, as well as the polygenic aspect of this pathology and the importance of cascadescreening of the FH patient’s healthy family members. This review article details different genetic techniques that can be used in FH identification when there is a clinical FH suspicion based on criteria comprised in prognosis scores, knowing that none of these are exhaustive inthe diagnosis, yet they efficaciously overlap and complement each other for confirming the disease at the molecular level. (Anatol J Cardiol2020; 23: 120-7)