A holistic approach to maximise diagnostic output in trio exome sequencing
IntroductionRare genetic diseases are a major cause for severe illness in children. Whole exome sequencing (WES) is a powerful tool for identifying genetic causes of rare diseases. For a better and faster assessment of the vast number of variants that are identified in the index patient in WES, pare...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1183891/full |
| _version_ | 1797823434850304000 |
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| author | Sandra von Hardenberg Hannah Wallaschek Chen Du Gunnar Schmidt Bernd Auber |
| author_facet | Sandra von Hardenberg Hannah Wallaschek Chen Du Gunnar Schmidt Bernd Auber |
| author_sort | Sandra von Hardenberg |
| collection | DOAJ |
| description | IntroductionRare genetic diseases are a major cause for severe illness in children. Whole exome sequencing (WES) is a powerful tool for identifying genetic causes of rare diseases. For a better and faster assessment of the vast number of variants that are identified in the index patient in WES, parental sequencing can be applied (“trio WES”).MethodsWe assessed the diagnostic rate of routine trio WES including analysis of copy number variants in 224 pediatric patients during an evaluation period of three years.ResultsTrio WES provided a diagnosis in 67 (30%) of all 224 analysed children. The turnaround time of trio WES analysis has been reduced significantly from 41 days in 2019 to 23 days in 2021. Copy number variants could be identified to be causative in 10 cases (4.5%), underlying the importance of copy number variant analysis. Variants in three genes which were previously not associated with a clinical condition (GAD1, TMEM222 and ZNFX1) were identified using the matching tool GeneMatcher and were part of the first description of a new syndrome.DiscussionTrio WES has proven to have a high diagnostic yield and to shorten the process of identifying the correct diagnosis in paediatric patients. Re-evaluation of all 224 trio WES 1–3 years after initial analysis did not establish new diagnoses. Initiating (trio) WES as a first-tier diagnostics including copy number variant detection should be considered as early as possible, especially for children treated in ICU, if a monogenetic disease is suspected. |
| first_indexed | 2024-03-13T10:23:58Z |
| format | Article |
| id | doaj.art-896bf4e8faa345b8adbfceb60593f5b7 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-03-13T10:23:58Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-896bf4e8faa345b8adbfceb60593f5b72023-05-19T16:05:24ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-05-011110.3389/fped.2023.11838911183891A holistic approach to maximise diagnostic output in trio exome sequencingSandra von HardenbergHannah WallaschekChen DuGunnar SchmidtBernd AuberIntroductionRare genetic diseases are a major cause for severe illness in children. Whole exome sequencing (WES) is a powerful tool for identifying genetic causes of rare diseases. For a better and faster assessment of the vast number of variants that are identified in the index patient in WES, parental sequencing can be applied (“trio WES”).MethodsWe assessed the diagnostic rate of routine trio WES including analysis of copy number variants in 224 pediatric patients during an evaluation period of three years.ResultsTrio WES provided a diagnosis in 67 (30%) of all 224 analysed children. The turnaround time of trio WES analysis has been reduced significantly from 41 days in 2019 to 23 days in 2021. Copy number variants could be identified to be causative in 10 cases (4.5%), underlying the importance of copy number variant analysis. Variants in three genes which were previously not associated with a clinical condition (GAD1, TMEM222 and ZNFX1) were identified using the matching tool GeneMatcher and were part of the first description of a new syndrome.DiscussionTrio WES has proven to have a high diagnostic yield and to shorten the process of identifying the correct diagnosis in paediatric patients. Re-evaluation of all 224 trio WES 1–3 years after initial analysis did not establish new diagnoses. Initiating (trio) WES as a first-tier diagnostics including copy number variant detection should be considered as early as possible, especially for children treated in ICU, if a monogenetic disease is suspected.https://www.frontiersin.org/articles/10.3389/fped.2023.1183891/fulltrioWESCNVGeneMatcherre-evaluationdiagnostic odyssey |
| spellingShingle | Sandra von Hardenberg Hannah Wallaschek Chen Du Gunnar Schmidt Bernd Auber A holistic approach to maximise diagnostic output in trio exome sequencing Frontiers in Pediatrics trioWES CNV GeneMatcher re-evaluation diagnostic odyssey |
| title | A holistic approach to maximise diagnostic output in trio exome sequencing |
| title_full | A holistic approach to maximise diagnostic output in trio exome sequencing |
| title_fullStr | A holistic approach to maximise diagnostic output in trio exome sequencing |
| title_full_unstemmed | A holistic approach to maximise diagnostic output in trio exome sequencing |
| title_short | A holistic approach to maximise diagnostic output in trio exome sequencing |
| title_sort | holistic approach to maximise diagnostic output in trio exome sequencing |
| topic | trioWES CNV GeneMatcher re-evaluation diagnostic odyssey |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1183891/full |
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