Detection of Disease-Causing SNVs/Indels and CNVs in Single Test Based on Whole Exome Sequencing : A Retrospective Case Study in Epileptic Encephalopathies
Copyright © 2021 Sun, Liu, Cai, Ma, Ni, Chen, Wang, Liu, Zhu, Liu and Zhu..
Background: Epileptic encephalopathies (EEs) are a pediatric entity with highly phenotypic and genetic heterogeneity. Both single nucleotide variants (SNVs)/Indels and copy number variations (CNVs) could be the causes. Whole exome sequencing (WES) is widely applied to detect SNVs/Indels, but the bioinformatics approach for detecting CNVs is still limited and weak. In the current study, the possibility of profiling both disease-causing SNVs/Indels and CNVs in a single test based on WES in EEs was evaluated. Methods: The infants diagnosed with EEs were enrolled from a single pediatric epilepsy center between January 2018 and February 2020. Demographic and clinical data were collected. In WES data, the pathogenic SNVs were identified through an in-house pipeline, and pathogenic CNVs were identified by CNVkit. The diagnostic rate was evaluated, and the molecular findings were characterized. Results: A total of 73 infants were included; 36 (49.32%) of them were males. The median age was 7 months. Thirty-two (43.84%) infants had been diagnosed with epilepsy syndrome. The most common type of syndrome was West syndrome (22/73, 30.1%), followed by Dravet syndrome (20/77, 27.4%). Fifty-four (73.97%) had intellectual development delay. The genetic cause of EEs, pathogenic or likely pathogenic variants, were successfully discovered in 46.6% (34/73) of the infants, and 29 (39.7%) infants carried SNVs/Indels, while 5 (6.8%) carried CNVs. The majority of the disease-causing variants were inherited in de novo pattern (25, 71.4%). In addition to showing that the variants in the ion channel encoding genes accounted for the main etiology, we discovered and confirmed two new disease-causing genes, CACNA1E and WDR26. Five discovered CNVs were deletions of 2q24.3, 1p36, 15q11-q13, 16p11.2, and 17p13.3, and all were confirmed by array comparative genomic hybridization. Conclusion: The application of both SNVs/Indels and CNVs detection in a single test based on WES yielded a high diagnosis rate in EEs. WES may serve as a first-tier test with cost-effective benefit in EEs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Frontiers in pediatrics - 9(2021) vom: 18., Seite 635703 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Dan [VerfasserIn] |
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| Links: |
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| Themen: |
Copy number variation |
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| Anmerkungen: |
Date Revised 01.06.2021 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fped.2021.635703 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM326043217 |
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| 245 | 1 | 0 | |a Detection of Disease-Causing SNVs/Indels and CNVs in Single Test Based on Whole Exome Sequencing |b A Retrospective Case Study in Epileptic Encephalopathies |
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| 520 | |a Copyright © 2021 Sun, Liu, Cai, Ma, Ni, Chen, Wang, Liu, Zhu, Liu and Zhu. | ||
| 520 | |a Background: Epileptic encephalopathies (EEs) are a pediatric entity with highly phenotypic and genetic heterogeneity. Both single nucleotide variants (SNVs)/Indels and copy number variations (CNVs) could be the causes. Whole exome sequencing (WES) is widely applied to detect SNVs/Indels, but the bioinformatics approach for detecting CNVs is still limited and weak. In the current study, the possibility of profiling both disease-causing SNVs/Indels and CNVs in a single test based on WES in EEs was evaluated. Methods: The infants diagnosed with EEs were enrolled from a single pediatric epilepsy center between January 2018 and February 2020. Demographic and clinical data were collected. In WES data, the pathogenic SNVs were identified through an in-house pipeline, and pathogenic CNVs were identified by CNVkit. The diagnostic rate was evaluated, and the molecular findings were characterized. Results: A total of 73 infants were included; 36 (49.32%) of them were males. The median age was 7 months. Thirty-two (43.84%) infants had been diagnosed with epilepsy syndrome. The most common type of syndrome was West syndrome (22/73, 30.1%), followed by Dravet syndrome (20/77, 27.4%). Fifty-four (73.97%) had intellectual development delay. The genetic cause of EEs, pathogenic or likely pathogenic variants, were successfully discovered in 46.6% (34/73) of the infants, and 29 (39.7%) infants carried SNVs/Indels, while 5 (6.8%) carried CNVs. The majority of the disease-causing variants were inherited in de novo pattern (25, 71.4%). In addition to showing that the variants in the ion channel encoding genes accounted for the main etiology, we discovered and confirmed two new disease-causing genes, CACNA1E and WDR26. Five discovered CNVs were deletions of 2q24.3, 1p36, 15q11-q13, 16p11.2, and 17p13.3, and all were confirmed by array comparative genomic hybridization. Conclusion: The application of both SNVs/Indels and CNVs detection in a single test based on WES yielded a high diagnosis rate in EEs. WES may serve as a first-tier test with cost-effective benefit in EEs | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Cai, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jiehui |e verfasserin |4 aut | |
| 700 | 1 | |a Ni, Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yongchu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yuanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhisheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Feng |e verfasserin |4 aut | |
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