{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:07:44Z","timestamp":1788584864032,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["EN 451-03-136\/2025-03\/200042"],"award-info":[{"award-number":["EN 451-03-136\/2025-03\/200042"]}]},{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["IIT-87939941"],"award-info":[{"award-number":["IIT-87939941"]}]},{"name":"Novartis","award":["EN 451-03-136\/2025-03\/200042"],"award-info":[{"award-number":["EN 451-03-136\/2025-03\/200042"]}]},{"name":"Novartis","award":["IIT-87939941"],"award-info":[{"award-number":["IIT-87939941"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>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\u2013phenotype 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&gt;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 &lt; 0.001), total cholesterol (TC) (p &lt; 0.001), low-density-lipoprotein cholesterol (LDL-C) (p &lt; 0.001) and triglyceridemia (p &lt; 0.001). 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.<\/jats:p>","DOI":"10.3390\/diagnostics15101212","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T04:21:23Z","timestamp":1747023683000},"page":"1212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Role of Next-Generation Sequencing in Diagnosis of Familial Hypercholesterolemia in Serbia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6290-0184","authenticated-orcid":false,"given":"Sandra Singh","family":"Lukac","sequence":"first","affiliation":[{"name":"Department for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Gasic","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0369-9729","authenticated-orcid":false,"given":"Jovana","family":"Komazec","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8352-0383","authenticated-orcid":false,"given":"Ivana","family":"Grubisa","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8627-9123","authenticated-orcid":false,"given":"Ljiljana","family":"Popovic","sequence":"additional","affiliation":[{"name":"Department for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4046-0562","authenticated-orcid":false,"given":"Iva","family":"Rasulic","sequence":"additional","affiliation":[{"name":"Department for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Pavlovic","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8070-1899","authenticated-orcid":false,"given":"Katarina","family":"Lalic","sequence":"additional","affiliation":[{"name":"Department for Lipid Disorders and Cardiovascular Complication in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.jacc.2018.05.044","article-title":"Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel","volume":"72","author":"Sturm","year":"2018","journal-title":"J. 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