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https://ahro.austin.org.au/austinjspui/handle/1/16129| Title: | Pitfalls in genetic testing: the story of missed SCN1A mutations | Austin 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 | Affiliation: | Austin Health, Heidelberg, Victoria, Australia Neurogenetics group, Department of Molecular Genetics, VIB, Antwerp, Belgium Laboratory of Neurogenetics Institute, Born-Bunge, University of Antwerp, Antwerp, Belgium Sorbonne universités, UPMC université Paris, Paris, France ICM, CNRS UMR 7225, Inserm U 1127, Paris, France Centre de reference épilepsies rares, Epilepsy unit, AP-HP Groupe hospitalier Pitié-Salpêtrière, Paris, France Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland Helsinki University Hospital, Helsinki, Finland Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands Department of Molecular Biology and Genetics, Bogaziçi University, Istanbul, Turkey Département de génétique, AP-HP, hôpital Pitié-Salpêtrière, Paris, France Department of Pediatric Neurology, Helsinki University Hospital, Helsinki, Finland Laboratory of Genetics, E.O. Ospedali Galliera, Genova, Italy Neurology Laboratory and Epilepsy Unit, Department of Neurology, Instituto de Investigatión Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain IIS-Fundación Jiménez Díaz and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA Wellcome Trust Sanger Institute, Hinxton, UK Pediatric Neurology and Neurogenetics Unit and Laboratories, A. Meyer Children's Hospital-University of Florence, Florence, Italy Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK The Epilepsy Society, Chalfont-St-Peter, Bucks, UK Department of Neurology, Danish Epilepsy Centre, Dianalund, Denmark Institute for Regional Health research, University of Southern Denmark, Odense, Denmark Folkhälsan Institute of Genetics, Helsinki, Finland Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland Institute of Human Genetics, University of Leipzig, Leipzig, Germany Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa ‘G. Gaslini’ Institute, Genova, Italy Laboratory of Neurogenetics, Department of Neurosciences, Giannina Gaslini Institute, Genova, Italy Department of Paediatrics, University of Melbourne and Royal Children's Hospital, Parkville, Victoria, Australia Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia Division of Neurology, Antwerp University Hospital, Antwerp, Belgium Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA GENOMED, Center for Medical Genetics, University of Antwerp, Antwerp, Belgium |
Issue Date: | Jul-2016 | Date: | 2016-04 | Publication information: | 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/16129 | DOI: | 10.1002/mgg3.217 | Journal: | Molecular Genetics & Genomic Medicine | PubMed URL: | https://pubmed.ncbi.nlm.nih.gov/27465585 | Type: | Journal Article | Subjects: | Dravet syndrome Sanger sequencing Epilepsy Genetic screening Next‐generation sequencing |
| Appears in Collections: | Journal articles |
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