{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T23:28:28Z","timestamp":1763767708065,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005375","name":"Latvian Council of Science","doi-asserted-by":"publisher","award":["lzp-2020\/1-0151"],"award-info":[{"award-number":["lzp-2020\/1-0151"]}],"id":[{"id":"10.13039\/501100005375","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: There is limited data on the genetic characteristics of patients with familial hypercholesterolemia (FH) in Latvia. We aim to describe monogenic variants in patients from the Latvian Registry of FH (LRFH). Methods: Whole genome sequencing with 30\u00d7 coverage was performed in unrelated index cases from the LRFH and the Genome Database of Latvian Population. LDLR, APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, LIPA, LPA, CYP27A1, and APOE genes were analyzed. Only variants annotated as pathogenic (P) or likely pathogenic (LP) using the FH Variant Curation Expert Panel guidelines for LDLR and adaptations for APOB and PCSK9 were reported. Results: Among 163 patients, the mean highest documented LDL-cholesterol level was 7.47 \u00b1 1.60 mmol\/L, and 79.1% of patients had LDL-cholesterol \u22656.50 mmol\/L. A total of 15 P\/LP variants were found in 34 patients (diagnostic yield: 20.9%): 14 in the LDLR gene and 1 in the APOB gene. Additionally, 24, 54, and 13 VUS were detected in LDLR, APOB, and PCSK9, respectively. No P\/LP variants were identified in the other tested genes. Conclusions: Despite the high clinical likelihood of FH, confirmed P\/LP variants were detected in only 20.9% of patients in the Latvian cohort when assessed with genome-wide next generation sequencing.<\/jats:p>","DOI":"10.3390\/jcm12155160","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T06:38:48Z","timestamp":1691390328000},"page":"5160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1322-7920","authenticated-orcid":false,"given":"Gustavs","family":"Latkovskis","sequence":"first","affiliation":[{"name":"Institute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, Latvia"},{"name":"Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia"},{"name":"Faculty of Medicine, University of Latvia, LV-1004 Riga, Latvia"}]},{"given":"Raimonds","family":"Rescenko-Krums","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}]},{"given":"Georgijs","family":"Nesterovics","sequence":"additional","affiliation":[{"name":"Institute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, Latvia"},{"name":"Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia"},{"name":"Faculty of Medicine, University of Latvia, LV-1004 Riga, Latvia"}]},{"given":"Monta","family":"Briviba","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}]},{"given":"Vita","family":"Saripo","sequence":"additional","affiliation":[{"name":"Institute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, Latvia"},{"name":"Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia"}]},{"given":"Dainus","family":"Gilis","sequence":"additional","affiliation":[{"name":"Institute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, Latvia"},{"name":"Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia"},{"name":"Faculty of Medicine, University of Latvia, LV-1004 Riga, Latvia"}]},{"given":"Elizabete","family":"Terauda","sequence":"additional","affiliation":[{"name":"Institute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, Latvia"},{"name":"Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia"},{"name":"Faculty of Medicine, University of Latvia, LV-1004 Riga, Latvia"}]},{"given":"Ruta","family":"Meiere","sequence":"additional","affiliation":[{"name":"Institute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, Latvia"},{"name":"Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9850-7891","authenticated-orcid":false,"given":"Gunda","family":"Skudrina","sequence":"additional","affiliation":[{"name":"Institute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, Latvia"},{"name":"Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia"}]},{"given":"Andrejs","family":"Erglis","sequence":"additional","affiliation":[{"name":"Institute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, Latvia"},{"name":"Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia"},{"name":"Faculty of Medicine, University of Latvia, LV-1004 Riga, Latvia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4942-1730","authenticated-orcid":false,"given":"Joana Rita","family":"Chora","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Prevention of Noncommunicable Diseases, National Institute of Health Dr. Ricardo Jorge, 164-9016 Lisbon, Portugal"},{"name":"Department of Chemistry and Biochemistry, BioISI\u2014BioSystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1649-004 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8843-3799","authenticated-orcid":false,"given":"Mafalda","family":"Bourbon","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Prevention of Noncommunicable Diseases, National Institute of Health Dr. Ricardo Jorge, 164-9016 Lisbon, Portugal"},{"name":"Department of Chemistry and Biochemistry, BioISI\u2014BioSystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1649-004 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8362-5505","authenticated-orcid":false,"given":"Janis","family":"Klovins","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,7]]},"reference":[{"key":"ref_1","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":"Nordestgaard","year":"2013","journal-title":"Eur. 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