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American Journal of Human Genetics

Publication date: 2001-06-01
Volume: 68 Pages: 1327 - 32
Publisher: Elsevier (Cell Press)

Author:

Claes, Lieve
Del-Favero, J ; Ceulemans, B ; Lagae, Lieven ; Van Broeckhoven, C ; De Jonghe, P

Keywords:

Amino Acid Sequence, Base Sequence, Belgium, Child, Child, Preschool, Codon, Nonsense, Conserved Sequence, DNA Mutational Analysis, Epilepsies, Myoclonic, Exons, Female, Frameshift Mutation, Humans, Infant, Introns, Male, Microsatellite Repeats, Molecular Sequence Data, Mutation, Mutation, Missense, Nerve Tissue Proteins, Paternity, Phenotype, Polymorphism, Restriction Fragment Length, Sodium Channels, Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, FEBRILE SEIZURES PLUS, GENERALIZED EPILEPSY, POLYMORPHISMS, NAV1.1 Voltage-Gated Sodium Channel, 06 Biological Sciences, 11 Medical and Health Sciences, 31 Biological sciences, 32 Biomedical and clinical sciences, 42 Health sciences

Abstract:

Severe myoclonic epilepsy of infancy (SMEI) is a rare disorder that occurs in isolated patients. The disease is characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex partial seizures. Psychomotor development stagnates around the second year of life. Missense mutations in the gene that codes for a neuronal voltage-gated sodium-channel alpha-subunit (SCN1A) were identified in families with generalized epilepsy with febrile seizures plus (GEFS+). GEFS+ is a mild type of epilepsy associated with febrile and afebrile seizures. Because both GEFS+ and SMEI involve fever-associated seizures, we screened seven unrelated patients with SMEI for mutations in SCN1A. We identified a mutation in each patient: four had frameshift mutations, one had a nonsense mutation, one had a splice-donor mutation, and one had a missense mutation. All mutations are de novo mutations and were not observed in 184 control chromosomes.