Open AccessPitfalls in genetic testing: the story of missed SCN1A mutations
Author(s) -
Djémié Tania,
Weckhuysen Sarah,
Spiczak Sarah,
Carvill Gemma L.,
Jaehn Johanna,
Anttonen AnnaKaisa,
Brilstra Eva,
Caglayan Hande S.,
Kovel Carolien G.,
Depienne Christel,
Gaily Eija,
Gennaro Elena,
Giraldez Beatriz G.,
Gormley Padhraig,
GuerreroLópez Rosa,
Guerrini Renzo,
Hämäläinen Eija,
Hartmann Corinna,
HernandezHernandez Laura,
Hjalgrim Helle,
Koeleman Bobby P. C.,
Leguern Eric,
Lehesjoki AnnaElina,
Lemke Johannes R.,
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,
Kempen Marjan J. A.,
Verbeek Nienke E.,
Usluer Sunay,
Zara Federico,
Palotie Aarno,
Mefford Heather C.,
Scheffer Ingrid E.,
De Jonghe Peter,
Helbig Ingo,
Suls Arvid
Publication year - 2016
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.217
Subject(s) - sanger sequencing , dravet syndrome , dna sequencing , genetic testing , mutation , medicine , genetics , computational biology , genetic diagnosis , bioinformatics , epilepsy , biology , gene , psychiatry
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 SCN 1A , the major gene implicated in epilepsy, are found in the majority of Dravet syndrome ( DS ) patients, we focused on missed SCN 1A mutations. Methods We sent out a survey to 16 genetic centers performing SCN 1A testing. Results We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN 1A mutation‐negative, both due to technical limitations and human errors. Conclusion We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN 1A mutations are an even more frequent cause of DS than already anticipated.