title: Confirming the recessive inheritance of SCN1B mutations in developmental epileptic encephalopathy.
abstract: Dominant SCN1B mutations are known to cause several epilepsy syndromes in humans. Only 2 epilepsy patients to date have been reported to have recessive mutations in SCN1B as the likely cause of their phenotype. Here, we confirm the recessive inheritance of 2 novel SCN1B mutations in 5 children from 3 families with developmental epileptic encephalopathy. The recessive inheritance and early death in these patients is consistent with the Dravet-like phenotype observed in Scn1b-/-mice. The 'negative' clinical exome in one of these families highlights the need to consider recessive mutations in the interpretation of variants in typically dominant genes.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: W
authors.initials: W
authors.lastname: Ramadan
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: N
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Anazi
authors.affiliation: Department of Pediatrics, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
authors.forename: A Y
authors.initials: AY
authors.lastname: Kentab
authors.affiliation: Department of Pediatrics, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
authors.forename: F A
authors.initials: FA
authors.lastname: Bashiri
authors.affiliation: Department of Pediatrics, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
authors.forename: M H
authors.initials: MH
authors.lastname: Hamad
authors.affiliation: Department of Pediatric Subspecialties, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: L
authors.initials: L
authors.lastname: Jad
authors.affiliation: Department of Pediatrics, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
authors.forename: M A
authors.initials: MA
authors.lastname: Salih
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: H
authors.initials: H
authors.lastname: Alsaif
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Hashem
authors.affiliation: Department of Pediatric Subspecialties, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: E
authors.initials: E
authors.lastname: Faqeih
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: H E
authors.initials: HE
authors.lastname: Shamseddin
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: F S
authors.identifier: http://orcid.org/0000-0003-4158-341X
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D017809:Fatal Outcome; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D062547:Voltage-Gated Sodium Channel beta-1 Subunit / Q000235:genetics*
chemical_list: D015415:Biomarkers; C470379:SCN1B protein, human; D062547:Voltage-Gated Sodium Channel beta-1 Subunit
keywords: 
  SCN1B
  ; GEFS+; clinical exome; epilepsy; haploinsufficiency; homozygous mutation; voltage-gated sodium channel