Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing
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× coverage was performed in unrelated inde...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/15/5160 |
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| author | Gustavs Latkovskis Raimonds Rescenko-Krums Georgijs Nesterovics Monta Briviba Vita Saripo Dainus Gilis Elizabete Terauda Ruta Meiere Gunda Skudrina Andrejs Erglis Joana Rita Chora Mafalda Bourbon Janis Klovins |
| author_facet | Gustavs Latkovskis Raimonds Rescenko-Krums Georgijs Nesterovics Monta Briviba Vita Saripo Dainus Gilis Elizabete Terauda Ruta Meiere Gunda Skudrina Andrejs Erglis Joana Rita Chora Mafalda Bourbon Janis Klovins |
| author_sort | Gustavs Latkovskis |
| collection | DOAJ |
| description | 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× coverage was performed in unrelated index cases from the LRFH and the Genome Database of Latvian Population. <i>LDLR</i>, <i>APOB</i>, <i>PCSK9</i>, <i>LDLRAP1</i>, <i>ABCG5</i>, <i>ABCG8</i>, <i>LIPA</i>, <i>LPA</i>, <i>CYP27A1</i>, and <i>APOE</i> genes were analyzed. Only variants annotated as pathogenic (P) or likely pathogenic (LP) using the FH Variant Curation Expert Panel guidelines for <i>LDLR</i> and adaptations for <i>APOB</i> and <i>PCSK9</i> were reported. Results: Among 163 patients, the mean highest documented LDL-cholesterol level was 7.47 ± 1.60 mmol/L, and 79.1% of patients had LDL-cholesterol ≥6.50 mmol/L. A total of 15 P/LP variants were found in 34 patients (diagnostic yield: 20.9%): 14 in the <i>LDLR</i> gene and 1 in the <i>APOB</i> gene. Additionally, 24, 54, and 13 VUS were detected in <i>LDLR, APOB,</i> and <i>PCSK9</i>, 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. |
| first_indexed | 2024-03-11T00:23:49Z |
| format | Article |
| id | doaj.art-ca0ae898dbf945d5b2b8a271439d2e48 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-11T00:23:49Z |
| publishDate | 2023-08-01 |
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| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-ca0ae898dbf945d5b2b8a271439d2e482023-11-18T23:10:10ZengMDPI AGJournal of Clinical Medicine2077-03832023-08-011215516010.3390/jcm12155160Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide SequencingGustavs Latkovskis0Raimonds Rescenko-Krums1Georgijs Nesterovics2Monta Briviba3Vita Saripo4Dainus Gilis5Elizabete Terauda6Ruta Meiere7Gunda Skudrina8Andrejs Erglis9Joana Rita Chora10Mafalda Bourbon11Janis Klovins12Institute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, LatviaLatvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaInstitute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, LatviaLatvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaInstitute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, LatviaInstitute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, LatviaInstitute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, LatviaInstitute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, LatviaInstitute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, LatviaInstitute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, LatviaDepartment of Health Promotion and Prevention of Noncommunicable Diseases, National Institute of Health Dr. Ricardo Jorge, 164-9016 Lisbon, PortugalDepartment of Health Promotion and Prevention of Noncommunicable Diseases, National Institute of Health Dr. Ricardo Jorge, 164-9016 Lisbon, PortugalLatvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaBackground: 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× coverage was performed in unrelated index cases from the LRFH and the Genome Database of Latvian Population. <i>LDLR</i>, <i>APOB</i>, <i>PCSK9</i>, <i>LDLRAP1</i>, <i>ABCG5</i>, <i>ABCG8</i>, <i>LIPA</i>, <i>LPA</i>, <i>CYP27A1</i>, and <i>APOE</i> genes were analyzed. Only variants annotated as pathogenic (P) or likely pathogenic (LP) using the FH Variant Curation Expert Panel guidelines for <i>LDLR</i> and adaptations for <i>APOB</i> and <i>PCSK9</i> were reported. Results: Among 163 patients, the mean highest documented LDL-cholesterol level was 7.47 ± 1.60 mmol/L, and 79.1% of patients had LDL-cholesterol ≥6.50 mmol/L. A total of 15 P/LP variants were found in 34 patients (diagnostic yield: 20.9%): 14 in the <i>LDLR</i> gene and 1 in the <i>APOB</i> gene. Additionally, 24, 54, and 13 VUS were detected in <i>LDLR, APOB,</i> and <i>PCSK9</i>, 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.https://www.mdpi.com/2077-0383/12/15/5160familial hypercholesterolemialow-density lipoprotein cholesterolgenetic studymonogenicwhole-genome sequencingregistry |
| spellingShingle | Gustavs Latkovskis Raimonds Rescenko-Krums Georgijs Nesterovics Monta Briviba Vita Saripo Dainus Gilis Elizabete Terauda Ruta Meiere Gunda Skudrina Andrejs Erglis Joana Rita Chora Mafalda Bourbon Janis Klovins Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing Journal of Clinical Medicine familial hypercholesterolemia low-density lipoprotein cholesterol genetic study monogenic whole-genome sequencing registry |
| title | Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing |
| title_full | Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing |
| title_fullStr | Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing |
| title_full_unstemmed | Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing |
| title_short | Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing |
| title_sort | genetic characteristics of latvian patients with familial hypercholesterolemia the first analysis from genome wide sequencing |
| topic | familial hypercholesterolemia low-density lipoprotein cholesterol genetic study monogenic whole-genome sequencing registry |
| url | https://www.mdpi.com/2077-0383/12/15/5160 |
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