Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in Serbia
Sandra Singh Lukac,
Vladimir Gasic,
Jovana Komazec,
Ivana Grubisa,
Ljiljana Popovic,
Iva Rasulic,
Sonja Pavlovic,
Katarina Lalic
Affiliations
Sandra Singh Lukac
Department for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
Vladimir Gasic
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia
Jovana Komazec
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia
Ivana Grubisa
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia
Ljiljana Popovic
Department for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
Iva Rasulic
Department for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
Sonja Pavlovic
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia
Katarina Lalic
Department for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
Objectives: 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 LDLR, APOB, PCSK9 and LDLRAP1 genes and to identify the genotype–phenotype correlation in Serbian FH patients. Method: 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. Results: An overall mutation detection rate of 43.6% was achieved. Thirteen distinct variants were detected in the LDLR 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 APOB gene. No pathogenic variants were detected in the PCSK9 or LDLRAP1 genes. Comparing genetically FH-positive and FH-negative patients, statistical significance was observed in terms of age (p p p p Conclusions: 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 LDLR gene were distributed across nearly all exons, the FH diagnostics in Serbia ought to be based on NGS methodology.
