Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in Serbia
<b data-eusoft-scrollable-element="1">Objectives:</b> 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 <i data-eusoft-scrollabl...
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| author | Sandra Singh Lukac Vladimir Gasic Jovana Komazec Ivana Grubisa Ljiljana Popovic Iva Rasulic Sonja Pavlovic Katarina Lalic |
| author_facet | Sandra Singh Lukac Vladimir Gasic Jovana Komazec Ivana Grubisa Ljiljana Popovic Iva Rasulic Sonja Pavlovic Katarina Lalic |
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| description | <b data-eusoft-scrollable-element="1">Objectives:</b> 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 <i data-eusoft-scrollable-element="1">LDLR</i>, <i data-eusoft-scrollable-element="1">APOB</i>, <i data-eusoft-scrollable-element="1">PCSK9</i> and <i data-eusoft-scrollable-element="1">LDLRAP1</i> genes and to identify the genotype–phenotype correlation in Serbian FH patients. <b data-eusoft-scrollable-element="1">Method:</b> 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. <b data-eusoft-scrollable-element="1">Results:</b> An overall mutation detection rate of 43.6% was achieved. Thirteen distinct variants were detected in the <i data-eusoft-scrollable-element="1">LDLR</i> 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 <i data-eusoft-scrollable-element="1">APOB</i> gene. No pathogenic variants were detected in the <i data-eusoft-scrollable-element="1">PCSK9</i> or <i data-eusoft-scrollable-element="1">LDLRAP1</i> genes. Comparing genetically FH-positive and FH-negative patients, statistical significance was observed in terms of age (<i data-eusoft-scrollable-element="1">p</i> < 0.001), total cholesterol (TC) (<i data-eusoft-scrollable-element="1">p</i> < 0.001), low-density-lipoprotein cholesterol (LDL-C) (<i data-eusoft-scrollable-element="1">p</i> < 0.001) and triglyceridemia (<i data-eusoft-scrollable-element="1">p</i> < 0.001). <b data-eusoft-scrollable-element="1">Conclusions:</b> 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 <i data-eusoft-scrollable-element="1">LDLR</i> gene were distributed across nearly all exons, the FH diagnostics in Serbia ought to be based on NGS methodology. |
| format | Article |
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| spelling | doaj-art-1a7fe3d99c474eb2a7dd1eb0cfb5dfd62025-08-20T03:14:31ZengMDPI AGDiagnostics2075-44182025-05-011510121210.3390/diagnostics15101212Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in SerbiaSandra Singh Lukac0Vladimir Gasic1Jovana Komazec2Ivana Grubisa3Ljiljana Popovic4Iva Rasulic5Sonja Pavlovic6Katarina Lalic7Department for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, SerbiaInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, SerbiaInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, SerbiaInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, SerbiaDepartment for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, SerbiaDepartment for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, SerbiaInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, SerbiaDepartment for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, Serbia<b data-eusoft-scrollable-element="1">Objectives:</b> 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 <i data-eusoft-scrollable-element="1">LDLR</i>, <i data-eusoft-scrollable-element="1">APOB</i>, <i data-eusoft-scrollable-element="1">PCSK9</i> and <i data-eusoft-scrollable-element="1">LDLRAP1</i> genes and to identify the genotype–phenotype correlation in Serbian FH patients. <b data-eusoft-scrollable-element="1">Method:</b> 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. <b data-eusoft-scrollable-element="1">Results:</b> An overall mutation detection rate of 43.6% was achieved. Thirteen distinct variants were detected in the <i data-eusoft-scrollable-element="1">LDLR</i> 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 <i data-eusoft-scrollable-element="1">APOB</i> gene. No pathogenic variants were detected in the <i data-eusoft-scrollable-element="1">PCSK9</i> or <i data-eusoft-scrollable-element="1">LDLRAP1</i> genes. Comparing genetically FH-positive and FH-negative patients, statistical significance was observed in terms of age (<i data-eusoft-scrollable-element="1">p</i> < 0.001), total cholesterol (TC) (<i data-eusoft-scrollable-element="1">p</i> < 0.001), low-density-lipoprotein cholesterol (LDL-C) (<i data-eusoft-scrollable-element="1">p</i> < 0.001) and triglyceridemia (<i data-eusoft-scrollable-element="1">p</i> < 0.001). <b data-eusoft-scrollable-element="1">Conclusions:</b> 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 <i data-eusoft-scrollable-element="1">LDLR</i> gene were distributed across nearly all exons, the FH diagnostics in Serbia ought to be based on NGS methodology.https://www.mdpi.com/2075-4418/15/10/1212familial hypercholesterolemiaNGS<i>LDLR</i> gene<i>APOB</i> gene |
| spellingShingle | Sandra Singh Lukac Vladimir Gasic Jovana Komazec Ivana Grubisa Ljiljana Popovic Iva Rasulic Sonja Pavlovic Katarina Lalic Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in Serbia Diagnostics familial hypercholesterolemia NGS <i>LDLR</i> gene <i>APOB</i> gene |
| title | Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in Serbia |
| title_full | Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in Serbia |
| title_fullStr | Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in Serbia |
| title_full_unstemmed | Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in Serbia |
| title_short | Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in Serbia |
| title_sort | role of next generation sequencing in diagnosis of familial hypercholesterolemia in serbia |
| topic | familial hypercholesterolemia NGS <i>LDLR</i> gene <i>APOB</i> gene |
| url | https://www.mdpi.com/2075-4418/15/10/1212 |
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