BACKGROUND: Sodium channel alpha 1 subunit gene, SCN1A, is the gene encoding the neuronal voltage-gated sodium channel alpha 1 subunit (Na(v)1.1) and is mutated in different forms of epilepsy. Mutations in this gene were observed in more than 70% of patients with severe myoclonic epilepsy of infancy (SMEI) and were also found in different types of infantile epileptic encephalopathy. OBJECTIVE: To search for disease-causing mutations in SCN1A in patients with cryptogenic epileptic syndromes (ie, syndromes with an unknown cause). DESIGN: Clinical characterization and molecular genetic analysis of a cohort of patients. SETTING: University hospitals, rehabilitation centers, and molecular biology laboratories. PATIENTS: Sixty unrelated patients with cryptogenic epileptic syndromes. MAIN OUTCOME MEASURES: Samples of DNA were analyzed for mutations and for large heterozygous deletions encompassing the SCN1A gene. A search for microdeletions in the SCN1A gene was also performed in the subset of patients with SMEI/SMEI-borderland who had negative results at the point mutation screening. RESULTS: No large deletions at the SCN1A locus were found in any of the patients analyzed. In contrast, 13 different point mutations were identified in 12 patients: 10 with SMEI, 1 with generalized epilepsy with febrile seizures plus, and 1 with cryptogenic focal epilepsy. An additional search for SCN1A intragenic microdeletions in the remaining patients with SMEI/SMEI-borderland and no point mutations was also negative. CONCLUSIONS: These results confirm the role of the SCN1A gene in different types of epilepsy, including cryptogenic epileptic syndromes. However, large deletions encompassing SCN1A were not common disease-causing rearrangements in this group of epilepsies.
BACKGROUND:Sodium channel alpha 1 subunit gene, SCN1A, is the gene encoding the neuronal voltage-gated sodium channel alpha 1 subunit (Na(v)1.1) and is mutated in different forms of epilepsy. Mutations in this gene were observed in more than 70% of patients with severe myoclonic epilepsy of infancy (SMEI) and were also found in different types of infantile epileptic encephalopathy. OBJECTIVE: To search for disease-causing mutations in SCN1A in patients with cryptogenic epileptic syndromes (ie, syndromes with an unknown cause). DESIGN: Clinical characterization and molecular genetic analysis of a cohort of patients. SETTING: University hospitals, rehabilitation centers, and molecular biology laboratories. PATIENTS: Sixty unrelated patients with cryptogenic epileptic syndromes. MAIN OUTCOME MEASURES: Samples of DNA were analyzed for mutations and for large heterozygous deletions encompassing the SCN1A gene. A search for microdeletions in the SCN1A gene was also performed in the subset of patients with SMEI/SMEI-borderland who had negative results at the point mutation screening. RESULTS: No large deletions at the SCN1A locus were found in any of the patients analyzed. In contrast, 13 different point mutations were identified in 12 patients: 10 with SMEI, 1 with generalized epilepsy with febrile seizures plus, and 1 with cryptogenic focal epilepsy. An additional search for SCN1A intragenic microdeletions in the remaining patients with SMEI/SMEI-borderland and no point mutations was also negative. CONCLUSIONS: These results confirm the role of the SCN1A gene in different types of epilepsy, including cryptogenic epileptic syndromes. However, large deletions encompassing SCN1A were not common disease-causing rearrangements in this group of epilepsies.
Authors: Xiaoyang Cheng; Sulayman D Dib-Hajj; Lynda Tyrrell; Dowain A Wright; Tanya Z Fischer; Stephen G Waxman Journal: Mol Pain Date: 2010-04-29 Impact factor: 3.395
Authors: Ana Carla Mondek Rampazzo; Rafael Rodrigues Pinheiro Dos Santos; Fernando Arfux Maluf; Renata Faria Simm; Fernando Augusto Lima Marson; Manoela Marques Ortega; Paulo Henrique Pires de Aguiar Journal: Neurogenetics Date: 2021-05-03 Impact factor: 2.660
Authors: Claudia B Catarino; Joan Y W Liu; Ioannis Liagkouras; Vaneesha S Gibbons; Robyn W Labrum; Rachael Ellis; Cathy Woodward; Mary B Davis; Shelagh J Smith; J Helen Cross; Richard E Appleton; Simone C Yendle; Jacinta M McMahon; Susannah T Bellows; Thomas S Jacques; Sameer M Zuberi; Matthias J Koepp; Lillian Martinian; Ingrid E Scheffer; Maria Thom; Sanjay M Sisodiya Journal: Brain Date: 2011-06-29 Impact factor: 13.501