{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T18:19:10Z","timestamp":1783621150293,"version":"3.55.0"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education, Science and Innovation of the Republic Uzbekistan","award":["State Registration No. AL-8223092044"],"award-info":[{"award-number":["State Registration No. AL-8223092044"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Background<\/jats:title>\n \n Familial hypercholesterolaemia (FH) is an inherited disorder with markedly elevated LDL-C and increased risk of premature atherosclerotic cardiovascular disease, most often caused by pathogenic variants in\n LDLR<\/jats:italic>\n and less frequently\n APOB<\/jats:italic>\n \/\n PCSK9<\/jats:italic>\n (or recessive\n LDLRAP1<\/jats:italic>\n ). FH is commonly assessed using the Dutch Lipid Clinic Network (DLCN) score (definite >8, probable 6\u20138, possible 3\u20135). In Uzbekistan, genetic evidence for FH remains limited and largely based on candidate-variant studies, and the diagnostic yield of NGS for monogenic FH in CAD patients is not well defined.\n <\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n For the first time in Uzbekistan and Central Asia, to investigate FH-associated monogenic variants using next-generation sequencing (NGS) and to assess the validity of the DLCN criteria against genetic testing as the diagnostic reference standard in Uzbek patients with CAD and suspected FH.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This study included 95 patients with coronary artery disease (CAD) who underwent targeted NGS of\n LDLR<\/jats:italic>\n ,\n APOB<\/jats:italic>\n ,\n PCSK9<\/jats:italic>\n , and\n LDLRAP1<\/jats:italic>\n . The suspected\/phenotypic FH group comprised 56 patients: 53 with DLCN-predicted heterozygous FH (HeFH)\u2014possible (3\u20135 points, n\u2009=\u200922), probable (6\u20138 points, n\u2009=\u200916), and definite (>8 points, n\u2009=\u200915)\u2014and 3 siblings from one family with a homozygous FH (HoFH) phenotype. The control group included 39 CAD patients with hypercholesterolemia without an FH diagnosis (DLCN 1\u20132 points). Only pathogenic\/likely pathogenic (P\/LP) variants were used for genetic confirmation of FH.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Pathogenic\/likely pathogenic variants were detected in 10\/53 (18.9%) DLCN-predicted HeFH patients and in all three HoFH siblings. Genetic confirmation rates (PPV) were 46.7% (7\/15) in definite HeFH, 12.5% (2\/16) in probable HeFH, and 4.5% (1\/22) in possible HeFH; no P\/LP variants were detected in controls (0\/39). Using a DLCN >8 threshold, sensitivity was 70.0% (7\/10) and specificity was 90.2% (74\/82) in the CAD cohort excluding the HoFH family.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n NGS confirmed the highest diagnostic yield in patients with DLCN >8, supporting its use as a practical threshold to prioritise genetic testing; however, monogenic FH may still be present in patients with probable or possible DLCN scores.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0353401","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:41:37Z","timestamp":1783618897000},"page":"e0353401","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic yield of next-generation sequencing for detecting monogenic familial hypercholesterolemia in uzbek patients with coronary artery disease"],"prefix":"10.1371","volume":"21","author":[{"given":"Rano B.","family":"Alieva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2354-1785","authenticated-orcid":true,"given":"Aleksandr B.","family":"Shek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiya V.","family":"Bahachova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khurshid G.","family":"Fozilov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guzal J.","family":"Abdullaeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisher A.","family":"Abdullaev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilya E.","family":"Kan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shavkat U.","family":"Khoshimov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey R.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulugbek I.","family":"Nizamov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilnora B.","family":"Yusupalieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"issue":"5","key":"pone.0353401.ref001","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/aje\/kwh237","article-title":"Familial hypercholesterolemia and coronary heart disease: A HuGE association review","volume":"160","author":"MA Austin","year":"2004","journal-title":"Am J Epidemiol"},{"issue":"45","key":"pone.0353401.ref002","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1093\/eurheartj\/eht273","article-title":"Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: Guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society","volume":"34","author":"BG Nordestgaard","year":"2013","journal-title":"Eur Heart J"},{"issue":"32","key":"pone.0353401.ref003","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1093\/eurheartj\/ehu274","article-title":"Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. 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