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Title: Pitfalls in genetic testing: the story of missed SCN1A mutations
Authors: Djémié, Tania;Weckhuysen, Sarah;von Spiczak, Sarah;Carvill, Gemma L;Jaehn, Johanna;Anttonen, Anna-Kaisa;Brilstra, Eva;Caglayan, Hande S;de Kovel, Carolien G;Depienne, Christel;Gaily, Eija;Gennaro, Elena;Giraldez, Beatriz G;Gormley, Padhraig;Guerrero-López, Rosa;Guerrini, Renzo;Hämäläinen, Eija;Hartmann, Corinna;Hernandez-Hernandez, Laura;Hjalgrim, Helle;Koeleman, Bobby PC;Leguern, Eric;Lehesjoki, Anna-Elina;Lemke, Johannes;Leu, Costin;Marini, Carla;McMahon, Jacinta M;Mei, Davide;Møller, Rikke S;Muhle, Hiltrud;Myers, Candace T;Nava, Caroline;Serratosa, Jose M;Sisodiya, Sanjay M;Stephani, Ulrich;Striano, Pasquale;van Kempen, Marjan JA;Verbeek, Nienke E;Usluer, Sunay;Zara, Federico;Palotie, Aarno;Mefford, Heather C;Scheffer, Ingrid E;De Jonghe, Peter;Helbig, Ingo;Suls, Arvid;EuroEPINOMICS‐RES Dravet working group
Issue Date: Jul-2016
EDate: 2016-04
Citation: Molecular Genetics & Genomic Medicine 2016; 14(4):457-464
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.
DOI: 10.1002/mgg3.217
PubMed URL:
Type: Journal Article
Subjects: Dravet syndrome
Sanger sequencing
Genetic screening
Next‐generation sequencing
Appears in Collections:Journal articles

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