@article{ae4dc3a1dd684d58a08dafe5b5128103,
title = "De novo SCN1A mutations in migrating partial seizures of infancy",
abstract = "Objective: To determine the genetic etiology of the severe early infantile onset syndrome of malignant migrating partial seizures of infancy (MPSI). Methods: Fifteen unrelated children with MPSI were screened for mutations in genes associated with infantile epileptic encephalopathies: SCN1A, CDKL5, STXBP1, PCDH19, and POLG. Microarray studies were performed to identify copy number variations. Results: One patient had a de novo SCN1A missense mutation p.R862G that affects the voltage sensor segment of SCN1A. A second patient had a de novo 11.06 Mb deletion of chromosome 2q24.2q31.1 encompassing more than 40 genes that included SCN1A. Screening of CDKL5 (13/15 patients), STXBP1 (13/15), PCDH19 (9/11 females), and the 3 common European mutations of POLG (11/15) was negative. Pathogenic copy number variations were not detected in 11/12 cases. Conclusion: Epilepsies associated with SCN1A mutations range in severity from febrile seizures to severe epileptic encephalopathies including Dravet syndrome and severe infantile multifocal epilepsy. MPSI is now the most severe SCN1A phenotype described to date. While not a common cause of MPSI, SCN1A screening should now be considered in patients with this devastating epileptic encephalopathy.",
author = "{Carranza Rojo}, D. and L. Hamiwka and McMahon, {J. M.} and Dibbens, {L. M.} and T. Arsov and A. Suls and T. St{\"o}dberg and K. Kelley and E. Wirrell and B. Appleton and M. MacKay and Freeman, {J. L.} and Yendle, {S. C.} and Berkovic, {S. F.} and T. Bienvenu and {De Jonghe}, P. and Thorburn, {D. R.} and Mulley, {J. C.} and Mefford, {H. C.} and Scheffer, {I. E.}",
note = "Funding Information: Dr. Carranza Rojo reports no disclosures. Dr. Hamiwka receives research support from the Epilepsy Foundation. J.M. McMahon reports no disclosures. Dr. Dibbens may accrue future revenue on a pending patent re: Therapeutic compound that relates to discovery of PCDH19 gene as the cause of familial epilepsy with mental retardation limited to females; and receives/has received research support from the National Health and Medical Research Council of Australia, the Thyne Reid Charitable Trusts, and the MS McLeod Trustees. Dr. Arsov, Dr. Suls, Dr. St{\"o}dberg, and Dr. Kelley report no disclosures. Dr. Wirrell serves on the editorial boards of Epilepsia , Canadian Journal of Neurological Sciences , and the Journal of Child Neurology ; and receives research support from the Mayo Foundation. Dr. Appleton has received funding for travel from UCB. Dr. Mackay has received speaker honoraria from UCB and Janssen-Cilag. Dr. Freeman and S.C. Yendle report no disclosures. Dr. Berkovic has served on scientific advisory boards for UCB and Janssen-Cilag; serves on the editorial boards of Lancet Neurology and Epileptic Disorders and the Advisory Board of Brain ; may accrue future revenue on a pending patent re: Therapeutic compound that relates to discovery of PCDH19 gene as the cause of familial epilepsy with mental retardation limited to females; has received speaker honoraria from UCB; has received unrestricted educational grants from UCB, Janssen-Cilag, and sanofi-aventis; and receives/has received research support from the National Health and Medical Research Council of Australia and The University of Melbourne. Dr. Bienvenu reports no disclosures. Dr. De Jonghe has received speaker honoraria from Biocodex; has received funding for travel from UCB and Biocodex; serves on the editorial board of Acta Neurologica Belgica ; and receives/has received research support from the National Fund for Scientific Research of Flanders, The University of Antwerp, and The Belgian Science and Policy Office. Dr. Thorburn serves on the editorial board of Mitochondrion and receives/has received support from the National Health and Medical Research Council of Australia, the Muscular Dystrophy Association (USA), The Juvenile Diabetes Research Foundation, the SMILE Foundation, the Jenour Foundation, the Australian Mitochondrial Disease Foundation, and the Foundation for Children. Dr. Mulley has served as a consultant for Athena Diagnostics; may accrue future revenue on a pending patent re: Therapeutic compound that relates to discovery of PCDH19 gene as the cause of familial epilepsy with mental retardation limited to females; and receives/has received research support from the National Health and Medical Research Council of Australia. Dr. Mefford receives research support from the NIH/NINDS and is a recipient of the Burroughs Wellcome Fund Career Award for Medical Scientists. Dr. Scheffer has served on scientific advisory boards for UCB and Janssen-Cilag EMEA; serves on the editorial boards of the Annals of Neurology and Epileptic Disorders ; may accrue future revenue on a pending patent re: Therapeutic compound that relates to discovery of PCDH19 gene as the cause of familial epilepsy with mental retardation limited to females; has received speaker honoraria from Athena Diagnostics, UCB, Janssen-Cilag EMEA, and Eli Lilly and Company; has received funding for travel from Athena Diagnostics, UCB, and Janssen-Cilag EMEA; and receives/has received research support from the National Health and Medical Research Council of Australia, Health Research Council of New Zealand, The University of Melbourne, American Epilepsy Society, the Jack Brockhoff Foundation, the Shepherd Foundation, and the Perpetual Charitable Trustees.",
year = "2011",
month = jul,
day = "26",
doi = "10.1212/WNL.0b013e318227046d",
language = "English (US)",
volume = "77",
pages = "380--383",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "4",
}