title: Homozygous mutations in the SCN1A gene associated with genetic epilepsy with febrile seizures plus and Dravet syndrome in 2 families.
abstract: BACKGROUND
  Mutations in the gene encoding the alpha subunit of the voltage-gated sodium channel SCN1A are associated with several epilepsy syndromes. These range from severe phenotypes including Dravet syndrome to milder phenotypes such as genetic epilepsy with febrile seizures plus (GEFS+). To date the sequence variants identified have been heterozygous in nature as one would expect for a disorder that occurs de novo or is dominantly inherited.
  
  
  RESULTS
  We report the association of two novel homozygous missense mutations of the SCN1A gene in four children with infantile epilepsies from two consanguineous pedigrees. We suggest that the nature and location of the identified amino acid changes allows heterozygous carriers to remain unaffected. However, having such changes on both alleles may have a cumulative and detrimental effect.
  
  
  CONCLUSIONS
  The presented cases illustrate how better understanding of the nature and location of SCN1A missense mutations may aid the interpretation of genotype-phenotype associations. SCN1A related epilepsies should be considered in children with infantile onset epilepsies even when an autosomal recessive neurological disorder is suspected.
authors: The Paediatric Neurosciences Research Group, Royal Hospital for Sick Children, Glasgow, UK; Developmental Neurosciences Programme at UCL-ICH, Great Ormond Street Hospital for Sick Children, London, UK.
authors: Andreas
authors: A
authors: Brunklaus
authors: The Paediatric Neurosciences Research Group, Royal Hospital for Sick Children, Glasgow, UK; Molecular Diagnostics, West of Scotland Genetic Services, Southern General Hospital, Glasgow, UK.
authors: Rachael
authors: R
authors: Ellis
authors: Department of Clinical Genetics, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK.
authors: Helen
authors: H
authors: Stewart
authors: Developmental Neurosciences Programme at UCL-ICH, Great Ormond Street Hospital for Sick Children, London, UK.
authors: Sarah
authors: S
authors: Aylett
authors: The Paediatric Neurosciences Research Group, Royal Hospital for Sick Children, Glasgow, UK; Molecular Diagnostics, West of Scotland Genetic Services, Southern General Hospital, Glasgow, UK.
authors: Eleanor
authors: E
authors: Reavey
authors: Royal Berkshire NHS Foundation Trust, Reading, UK.
authors: Ros
authors: R
authors: Jefferson
authors: Department of Paediatric Neurology, Children's Hospital, Oxford, UK.
authors: Rakesh
authors: R
authors: Jain
authors: Coventry and Warwickshire Partnership NHS Trust, Coventry, UK.
authors: Supratik
authors: S
authors: Chakraborty
authors: Department of Paediatric Neurology, Children's Hospital, Oxford, UK.
authors: Sandeep
authors: S
authors: Jayawant
authors: The Paediatric Neurosciences Research Group, Royal Hospital for Sick Children, Glasgow, UK; School of Medicine, College of Medical, Veterinary & Life Sciences, University of Glasgow, UK. Electronic address: sameer.zuberi@nhs.net.
authors: Sameer M
authors: SM
authors: Zuberi
mesh_terms: D002648:Child; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D003294:Seizures, Febrile / Q000235:genetics*; D013577:Syndrome
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel
keywords: Dravet syndrome; Febrile seizures; GEFS+; SCN1A; Severe myoclonic epilepsy of infancy