The use of next-generation sequencing in clinical diagnosis of familial hypercholesterolemia
PURPOSE: Familial hypercholesterolemia is a common Mendelian disorder associated with early-onset coronary heart disease that can be treated by cholesterol-lowering drugs. The majority of cases in the United Kingdom are currently without a molecular diagnosis, which is partly due to the cost and time associated with standard screening techniques. The main purpose of this study was to test the sensitivity and specificity of two next-generation sequencing protocols for genetic diagnosis of familial hypercholesterolemia.
METHODS: Libraries were prepared for next-generation sequencing by two target enrichment protocols; one using the SureSelect Target Enrichment System and the other using the PCR-based Access Array platform.
RESULTS: In the validation cohort, both protocols showed 100% specificity, whereas the sensitivity for short variant detection was 100% for the SureSelect Target Enrichment and 98% for the Access Array protocol. Large deletions/duplications were only detected using the SureSelect Target Enrichment protocol. In the prospective cohort, the mutation detection rate using the Access Array was highest in patients with clinically definite familial hypercholesterolemia (67%), followed by patients with possible familial hypercholesterolemia (26%).
CONCLUSION: We have shown the potential of target enrichment methods combined with next-generation sequencing for molecular diagnosis of familial hypercholesterolemia. Adopting these assays for patients with suspected familial hypercholesterolemia could improve cost-effectiveness and increase the overall number of patients with a molecular diagnosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Genetics in medicine : official journal of the American College of Medical Genetics - 15(2013), 12 vom: 25. Dez., Seite 948-57 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vandrovcova, Jana [VerfasserIn] |
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| Links: |
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| Themen: |
Evaluation Study |
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| Anmerkungen: |
Date Completed 14.07.2014 Date Revised 10.02.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/gim.2013.55 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM227561538 |
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| 245 | 1 | 4 | |a The use of next-generation sequencing in clinical diagnosis of familial hypercholesterolemia |
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| 500 | |a Date Completed 14.07.2014 | ||
| 500 | |a Date Revised 10.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: Familial hypercholesterolemia is a common Mendelian disorder associated with early-onset coronary heart disease that can be treated by cholesterol-lowering drugs. The majority of cases in the United Kingdom are currently without a molecular diagnosis, which is partly due to the cost and time associated with standard screening techniques. The main purpose of this study was to test the sensitivity and specificity of two next-generation sequencing protocols for genetic diagnosis of familial hypercholesterolemia | ||
| 520 | |a METHODS: Libraries were prepared for next-generation sequencing by two target enrichment protocols; one using the SureSelect Target Enrichment System and the other using the PCR-based Access Array platform | ||
| 520 | |a RESULTS: In the validation cohort, both protocols showed 100% specificity, whereas the sensitivity for short variant detection was 100% for the SureSelect Target Enrichment and 98% for the Access Array protocol. Large deletions/duplications were only detected using the SureSelect Target Enrichment protocol. In the prospective cohort, the mutation detection rate using the Access Array was highest in patients with clinically definite familial hypercholesterolemia (67%), followed by patients with possible familial hypercholesterolemia (26%) | ||
| 520 | |a CONCLUSION: We have shown the potential of target enrichment methods combined with next-generation sequencing for molecular diagnosis of familial hypercholesterolemia. Adopting these assays for patients with suspected familial hypercholesterolemia could improve cost-effectiveness and increase the overall number of patients with a molecular diagnosis | ||
| 650 | 4 | |a Evaluation Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Thomas, Ellen R A |e verfasserin |4 aut | |
| 700 | 1 | |a Atanur, Santosh S |e verfasserin |4 aut | |
| 700 | 1 | |a Norsworthy, Penny J |e verfasserin |4 aut | |
| 700 | 1 | |a Neuwirth, Clare |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Yvonne |e verfasserin |4 aut | |
| 700 | 1 | |a Kasperaviciute, Dalia |e verfasserin |4 aut | |
| 700 | 1 | |a Biggs, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Game, Laurence |e verfasserin |4 aut | |
| 700 | 1 | |a Mueller, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Soutar, Anne K |e verfasserin |4 aut | |
| 700 | 1 | |a Aitman, Timothy J |e verfasserin |4 aut | |
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