Pitfalls in genetic testing: the story of missed SCN1A mutations.
Ontology highlight
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.
SUBMITTER: Djemie T
PROVIDER: S-EPMC4947864 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
Pitfalls in genetic testing: the story of missed SCN1A mutations.
Djémié Tania T Weckhuysen Sarah S von Spiczak Sarah S Carvill Gemma L GL Jaehn Johanna J Anttonen Anna-Kaisa AK Brilstra Eva E Caglayan Hande S HS de Kovel Carolien G CG Depienne Christel C Gaily Eija E Gennaro Elena E Giraldez Beatriz G BG Gormley Padhraig P Guerrero-López Rosa R Guerrini Renzo R Hämäläinen Eija E Hartmann Corinna C Hernandez-Hernandez Laura L Hjalgrim Helle H Koeleman Bobby P C BP Leguern Eric E Lehesjoki Anna-Elina AE Lemke Johannes R JR Leu Costin C Marini Carla C McMahon Jacinta M JM Mei Davide D Møller Rikke S RS Muhle Hiltrud H Myers Candace T CT Nava Caroline C Serratosa Jose M JM Sisodiya Sanjay M SM Stephani Ulrich U Striano Pasquale P van Kempen Marjan J A MJ Verbeek Nienke E NE Usluer Sunay S Zara Federico F Palotie Aarno A Mefford Heather C HC Scheffer Ingrid E IE De Jonghe Peter P Helbig Ingo I Suls Arvid A
Molecular genetics & genomic medicine 20160414 4
<h4>Background</h4>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 implica ...[more]
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