Djémié, T;
Weckhuysen, S;
von Spiczak, S;
Carvill, GL;
Jaehn, J;
Anttonen, A-K;
Brilstra, E;
... EuroEPINOMICS‐RES Dravet working group; + view all
(2016)
Pitfalls in genetic testing: the story of missed SCN1A mutations.
Molecular Genetics & Genomic Medicine
, 4
(4)
pp. 457-464.
10.1002/mgg3.217.
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Abstract
BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated in epilepsy, are found in the majority of Dravet syndrome (DS) patients, we focused on missed SCN1A mutations. METHODS: We sent out a survey to 16 genetic centers performing SCN1A testing. RESULTS: We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN1A mutation-negative, both due to technical limitations and human errors. CONCLUSION: We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A mutations are an even more frequent cause of DS than already anticipated.
| Type: | Article |
|---|---|
| Title: | Pitfalls in genetic testing: the story of missed SCN1A mutations |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/mgg3.217 |
| Publisher version: | http://doi.org/10.1002/mgg3.217 |
| Language: | English |
| Additional information: | 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/ |
| Keywords: | Dravet syndrome, Sanger sequencing, epilepsy, genetic screening, next‐generation sequencing |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1508807 |
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