Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy
Background: The aim of this study was to explore the rare variants in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM). Methods: Forty-five unrelated probands with HCM were screened by targeted next generation sequencing (NGS) of 47 core and emerging genes connected with HCM....
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/10/12/1061 |
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| author | Miruna Mihaela Micheu Nicoleta-Monica Popa-Fotea Nicoleta Oprescu Stefan Bogdan Monica Dan Alexandru Deaconu Lucian Dorobantu Oana Gheorghe-Fronea Maria Greavu Corneliu Iorgulescu Alexandru Scafa-Udriste Razvan Ticulescu Radu Gabriel Vatasescu Maria Dorobanțu |
| author_facet | Miruna Mihaela Micheu Nicoleta-Monica Popa-Fotea Nicoleta Oprescu Stefan Bogdan Monica Dan Alexandru Deaconu Lucian Dorobantu Oana Gheorghe-Fronea Maria Greavu Corneliu Iorgulescu Alexandru Scafa-Udriste Razvan Ticulescu Radu Gabriel Vatasescu Maria Dorobanțu |
| author_sort | Miruna Mihaela Micheu |
| collection | DOAJ |
| description | Background: The aim of this study was to explore the rare variants in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM). Methods: Forty-five unrelated probands with HCM were screened by targeted next generation sequencing (NGS) of 47 core and emerging genes connected with HCM. Results: We identified 95 variants with allele frequency < 0.1% in population databases. MYBPC3 and TTN had the largest number of rare variants (17 variants each). A definite genetic etiology was found in 6 probands (13.3%), while inconclusive results due to either known or novel variants were established in 31 cases (68.9%). All disease-causing variants were detected in sarcomeric genes (MYBPC3 and MYH7 with two cases each, and one case in TNNI3 and TPM1 respectively). Multiple variants were detected in 27 subjects (60%), but no proband carried more than one causal variant. Of note, almost half of the rare variants were novel. Conclusions: Herein we reported for the first time the rare variants identified in core and putative genes associated with HCM in a cohort of Romanian unrelated adult patients. The clinical significance of most detected variants is yet to be established, additional studies based on segregation analysis being required for definite classification. |
| first_indexed | 2024-03-10T14:16:05Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T14:16:05Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-f0fb63f3ec084642b8cfc12da738ddcb2023-11-20T23:49:08ZengMDPI AGDiagnostics2075-44182020-12-011012106110.3390/diagnostics10121061Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic CardiomyopathyMiruna Mihaela Micheu0Nicoleta-Monica Popa-Fotea1Nicoleta Oprescu2Stefan Bogdan3Monica Dan4Alexandru Deaconu5Lucian Dorobantu6Oana Gheorghe-Fronea7Maria Greavu8Corneliu Iorgulescu9Alexandru Scafa-Udriste10Razvan Ticulescu11Radu Gabriel Vatasescu12Maria Dorobanțu13Department of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaMonza Hospital, Tony Bulandra Street, No. 27, 021967 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaMonza Hospital, Tony Bulandra Street, No. 27, 021967 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaDepartment of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, RomaniaBackground: The aim of this study was to explore the rare variants in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM). Methods: Forty-five unrelated probands with HCM were screened by targeted next generation sequencing (NGS) of 47 core and emerging genes connected with HCM. Results: We identified 95 variants with allele frequency < 0.1% in population databases. MYBPC3 and TTN had the largest number of rare variants (17 variants each). A definite genetic etiology was found in 6 probands (13.3%), while inconclusive results due to either known or novel variants were established in 31 cases (68.9%). All disease-causing variants were detected in sarcomeric genes (MYBPC3 and MYH7 with two cases each, and one case in TNNI3 and TPM1 respectively). Multiple variants were detected in 27 subjects (60%), but no proband carried more than one causal variant. Of note, almost half of the rare variants were novel. Conclusions: Herein we reported for the first time the rare variants identified in core and putative genes associated with HCM in a cohort of Romanian unrelated adult patients. The clinical significance of most detected variants is yet to be established, additional studies based on segregation analysis being required for definite classification.https://www.mdpi.com/2075-4418/10/12/1061hypertrophic cardiomyopathynext-generation sequencingrare genetic variants |
| spellingShingle | Miruna Mihaela Micheu Nicoleta-Monica Popa-Fotea Nicoleta Oprescu Stefan Bogdan Monica Dan Alexandru Deaconu Lucian Dorobantu Oana Gheorghe-Fronea Maria Greavu Corneliu Iorgulescu Alexandru Scafa-Udriste Razvan Ticulescu Radu Gabriel Vatasescu Maria Dorobanțu Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy Diagnostics hypertrophic cardiomyopathy next-generation sequencing rare genetic variants |
| title | Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy |
| title_full | Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy |
| title_fullStr | Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy |
| title_full_unstemmed | Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy |
| title_short | Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy |
| title_sort | yield of rare variants detected by targeted next generation sequencing in a cohort of romanian index patients with hypertrophic cardiomyopathy |
| topic | hypertrophic cardiomyopathy next-generation sequencing rare genetic variants |
| url | https://www.mdpi.com/2075-4418/10/12/1061 |
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