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The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia
Familial hypercholesterolemia (FH) is an autosomal dominant disorder. Although genetic testing is an important tool for detecting FH-causing mutations in patients, diagnostic methods for young patients with severe hypercholesterolemia are understudied. This study compares the target exome sequencing...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103295/ https://www.ncbi.nlm.nih.gov/pubmed/27830735 http://dx.doi.org/10.1038/srep36823 |
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author | Jiang, Long Wu, Wen-Feng Sun, Li-Yuan Chen, Pan-Pan Wang, Wei Benito-Vicente, Asier Zhang, Fan Pan, Xiao-Dong Cui, Wei Yang, Shi-Wei Zhou, Yu-Jie Martin, Cesar Wang, Lu-Ya |
author_facet | Jiang, Long Wu, Wen-Feng Sun, Li-Yuan Chen, Pan-Pan Wang, Wei Benito-Vicente, Asier Zhang, Fan Pan, Xiao-Dong Cui, Wei Yang, Shi-Wei Zhou, Yu-Jie Martin, Cesar Wang, Lu-Ya |
author_sort | Jiang, Long |
collection | PubMed |
description | Familial hypercholesterolemia (FH) is an autosomal dominant disorder. Although genetic testing is an important tool for detecting FH-causing mutations in patients, diagnostic methods for young patients with severe hypercholesterolemia are understudied. This study compares the target exome sequencing (TES) technique with the DNA resequencing array technique on young patients with severe hypercholesterolemia. A total of 20 unrelated patients (mean age 14.8 years) with total cholesterol > 10 mmol/L were included. 12 patient samples were processed by DNA resequencing array, 14 patient samples were processed by TES, and 6 patient samples were processed by both methods. Functional characterization of novel mutations was performed by flow cytometry. The mutation detection rate (MDR) of DNA resequencing array was 75%, while the MDR of TES was 100%. A total of 27 different mutations in the LDLR were identified, including 3 novel mutations and 8 mutations with previously unknown pathogenicity. Functional characterization of c.673delA, c.1363delC, p.Leu575Phe and p.Leu582Phe variants found that all of them are pathogenic. Additionally, 7 patients were diagnosed with Heterozygous FH (HeFH) in which lipid levels were significantly higher than common HeFH patients. This data indicates that TES is a very efficient tool for genetic diagnosis in young patients with severe hypercholesterolemia. |
format | Online Article Text |
id | pubmed-5103295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51032952016-11-17 The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia Jiang, Long Wu, Wen-Feng Sun, Li-Yuan Chen, Pan-Pan Wang, Wei Benito-Vicente, Asier Zhang, Fan Pan, Xiao-Dong Cui, Wei Yang, Shi-Wei Zhou, Yu-Jie Martin, Cesar Wang, Lu-Ya Sci Rep Article Familial hypercholesterolemia (FH) is an autosomal dominant disorder. Although genetic testing is an important tool for detecting FH-causing mutations in patients, diagnostic methods for young patients with severe hypercholesterolemia are understudied. This study compares the target exome sequencing (TES) technique with the DNA resequencing array technique on young patients with severe hypercholesterolemia. A total of 20 unrelated patients (mean age 14.8 years) with total cholesterol > 10 mmol/L were included. 12 patient samples were processed by DNA resequencing array, 14 patient samples were processed by TES, and 6 patient samples were processed by both methods. Functional characterization of novel mutations was performed by flow cytometry. The mutation detection rate (MDR) of DNA resequencing array was 75%, while the MDR of TES was 100%. A total of 27 different mutations in the LDLR were identified, including 3 novel mutations and 8 mutations with previously unknown pathogenicity. Functional characterization of c.673delA, c.1363delC, p.Leu575Phe and p.Leu582Phe variants found that all of them are pathogenic. Additionally, 7 patients were diagnosed with Heterozygous FH (HeFH) in which lipid levels were significantly higher than common HeFH patients. This data indicates that TES is a very efficient tool for genetic diagnosis in young patients with severe hypercholesterolemia. Nature Publishing Group 2016-11-10 /pmc/articles/PMC5103295/ /pubmed/27830735 http://dx.doi.org/10.1038/srep36823 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Jiang, Long Wu, Wen-Feng Sun, Li-Yuan Chen, Pan-Pan Wang, Wei Benito-Vicente, Asier Zhang, Fan Pan, Xiao-Dong Cui, Wei Yang, Shi-Wei Zhou, Yu-Jie Martin, Cesar Wang, Lu-Ya The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia |
title | The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia |
title_full | The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia |
title_fullStr | The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia |
title_full_unstemmed | The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia |
title_short | The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia |
title_sort | use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103295/ https://www.ncbi.nlm.nih.gov/pubmed/27830735 http://dx.doi.org/10.1038/srep36823 |
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