Verification of Underlying Genetic Cause in a Cohort of Russian Patients with Familial Hypercholesterolemia Using Targeted Next Generation Sequencing
Russian patients with familial hypercholesterolemia (FH) were screened for pathogenic mutations using targeted next generation sequencing. Genetic testing was performed in 52 probands with definite or probable FH based on the Dutch lipid clinic network criteria (DLCN score ≥ 6). Blood samples were s...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| Online Access: | https://www.mdpi.com/2308-3425/7/2/16 |
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| author | Anna E. Semenova Igor V. Sergienko Diego García-Giustiniani Lorenzo Monserrat Anna B. Popova Diana N. Nozadze Marat V. Ezhov |
| author_facet | Anna E. Semenova Igor V. Sergienko Diego García-Giustiniani Lorenzo Monserrat Anna B. Popova Diana N. Nozadze Marat V. Ezhov |
| author_sort | Anna E. Semenova |
| collection | DOAJ |
| description | Russian patients with familial hypercholesterolemia (FH) were screened for pathogenic mutations using targeted next generation sequencing. Genetic testing was performed in 52 probands with definite or probable FH based on the Dutch lipid clinic network criteria (DLCN score ≥ 6). Blood samples were studied by massive parallel sequencing (Illumina HiSeq 1500 platform) using a custom capture library related to dyslipidemia and premature atherosclerosis. Mutations considered to be responsible for monogenic FH were identified in 48% of the probands: 24 with mutations in the <i>LDLR</i> gene and two with a mutation in the <i>APOB</i> gene. There were 22 pathogenic/likely pathogenic mutations in <i>LDLR</i>, eight of which have not been previously described in the literature. Four patients with a clinical picture of homozygous FH had two heterozygous <i>LDLR</i> mutations. Although mutation-negative patients had highly elevated total cholesterol and low-density lipoprotein cholesterol levels, only half of them had a family history of hypercholesterolemia. With respect to heterozygous FH, mutation-positive patients had higher maximum total cholesterol levels (<i>p</i> = 0.01), more severe carotid atherosclerotic lesions, and a higher percentage of premature peripheral artery disease (<i>p</i> = 0.03) than mutation-negative ones. However, the number of patients who suffered from myocardial infarction was similar between the two groups. |
| first_indexed | 2024-03-10T19:49:44Z |
| format | Article |
| id | doaj.art-81f7dfdd74384bed81cfeb339cd78bd4 |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-10T19:49:44Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-81f7dfdd74384bed81cfeb339cd78bd42023-11-20T00:27:36ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252020-05-01721610.3390/jcdd7020016Verification of Underlying Genetic Cause in a Cohort of Russian Patients with Familial Hypercholesterolemia Using Targeted Next Generation SequencingAnna E. Semenova0Igor V. Sergienko1Diego García-Giustiniani2Lorenzo Monserrat3Anna B. Popova4Diana N. Nozadze5Marat V. Ezhov6National Medical Research Center of Cardiology, 121552 Moscow, RussiaNational Medical Research Center of Cardiology, 121552 Moscow, RussiaHealth in Code SL, Clinical Department, 15006 A Coruña, SpainHealth in Code SL, Clinical Department, 15006 A Coruña, SpainNational Medical Research Center of Cardiology, 121552 Moscow, RussiaNational Medical Research Center of Cardiology, 121552 Moscow, RussiaNational Medical Research Center of Cardiology, 121552 Moscow, RussiaRussian patients with familial hypercholesterolemia (FH) were screened for pathogenic mutations using targeted next generation sequencing. Genetic testing was performed in 52 probands with definite or probable FH based on the Dutch lipid clinic network criteria (DLCN score ≥ 6). Blood samples were studied by massive parallel sequencing (Illumina HiSeq 1500 platform) using a custom capture library related to dyslipidemia and premature atherosclerosis. Mutations considered to be responsible for monogenic FH were identified in 48% of the probands: 24 with mutations in the <i>LDLR</i> gene and two with a mutation in the <i>APOB</i> gene. There were 22 pathogenic/likely pathogenic mutations in <i>LDLR</i>, eight of which have not been previously described in the literature. Four patients with a clinical picture of homozygous FH had two heterozygous <i>LDLR</i> mutations. Although mutation-negative patients had highly elevated total cholesterol and low-density lipoprotein cholesterol levels, only half of them had a family history of hypercholesterolemia. With respect to heterozygous FH, mutation-positive patients had higher maximum total cholesterol levels (<i>p</i> = 0.01), more severe carotid atherosclerotic lesions, and a higher percentage of premature peripheral artery disease (<i>p</i> = 0.03) than mutation-negative ones. However, the number of patients who suffered from myocardial infarction was similar between the two groups.https://www.mdpi.com/2308-3425/7/2/16familial hypercholesterolemianext generation sequencingLDLRDutch lipid clinic network criteriacardiovascular risk |
| spellingShingle | Anna E. Semenova Igor V. Sergienko Diego García-Giustiniani Lorenzo Monserrat Anna B. Popova Diana N. Nozadze Marat V. Ezhov Verification of Underlying Genetic Cause in a Cohort of Russian Patients with Familial Hypercholesterolemia Using Targeted Next Generation Sequencing Journal of Cardiovascular Development and Disease familial hypercholesterolemia next generation sequencing LDLR Dutch lipid clinic network criteria cardiovascular risk |
| title | Verification of Underlying Genetic Cause in a Cohort of Russian Patients with Familial Hypercholesterolemia Using Targeted Next Generation Sequencing |
| title_full | Verification of Underlying Genetic Cause in a Cohort of Russian Patients with Familial Hypercholesterolemia Using Targeted Next Generation Sequencing |
| title_fullStr | Verification of Underlying Genetic Cause in a Cohort of Russian Patients with Familial Hypercholesterolemia Using Targeted Next Generation Sequencing |
| title_full_unstemmed | Verification of Underlying Genetic Cause in a Cohort of Russian Patients with Familial Hypercholesterolemia Using Targeted Next Generation Sequencing |
| title_short | Verification of Underlying Genetic Cause in a Cohort of Russian Patients with Familial Hypercholesterolemia Using Targeted Next Generation Sequencing |
| title_sort | verification of underlying genetic cause in a cohort of russian patients with familial hypercholesterolemia using targeted next generation sequencing |
| topic | familial hypercholesterolemia next generation sequencing LDLR Dutch lipid clinic network criteria cardiovascular risk |
| url | https://www.mdpi.com/2308-3425/7/2/16 |
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