Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in Serbia.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipid metabolism characterized by high levels of low-density lipoprotein (LDL). This study aimed to identify variants in the , , and genes and to identify the genotype-phenotype correlation in Serbian FH patients. This study included a total of 101 patients suspected of having FH based on clinical criteria. Genetic analysis was performed by the next-generation sequencing (NGS) method. An overall mutation detection rate of 43.6% was achieved. Thirteen distinct variants were detected in the gene (93.2%). The most frequently observed variant was c.858C>A p.(Ser286Arg), which was present in 26% of the LDLR-positive patients. Additional variants were detected in the gene. No pathogenic variants were detected in the or genes. Comparing genetically FH-positive and FH-negative patients, statistical significance was observed in terms of age ( < 0.001), total cholesterol (TC) ( < 0.001), low-density-lipoprotein cholesterol (LDL-C) ( < 0.001) and triglyceridemia ( < 0.001). This study represents the first insight into the genetic basis of FH in Serbia. Taking into consideration that variants were detected in more than one gene and that the variants in the gene were distributed across nearly all exons, the FH diagnostics in Serbia ought to be based on NGS methodology.