title: Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.
abstract: BACKGROUND
  Dravet syndrome is a severe form of epilepsy. Majority of patients have a mutation in SCN1A gene, which encodes a voltage-gated sodium channel. A recent study has demonstrated that 16% of SCN1A-negative patients have a mutation in PCDH19, the gene encoding protocadherin-19. Mutations in other genes account for only a very small proportion of families. TSPYL4 is a novel candidate gene within the locus 6q16.3-q22.31 identified by linkage study.
  
  
  OBJECTIVE
  The present study examined the mutations in epileptic Chinese children with emphasis on Dravet syndrome.
  
  
  METHODS
  A hundred children with severe epilepsy were divided into Dravet syndrome and non-Dravet syndrome groups and screened for SCN1A mutations by direct sequencing. SCN1A-negative Dravet syndrome patients and patients with phenotypes resembling Dravet syndrome were checked for PCDH19 and TSPYL4 mutations.
  
  
  RESULTS
  Eighteen patients (9 males, 9 females) were diagnosed to have Dravet syndrome. Among them, 83% (15/18) had SCN1A mutations including truncating (7), splice site (2) and missense mutations (6). The truncating/splice site mutations were associated with moderate to severe degree of intellectual disability (p<0.05). During the progression of disease, 73% (11/15) had features fitting into the diagnostic criteria of autism spectrum disorder and 53% (8/15) had history of vaccination-induced seizures. A novel PCDH19 p.D377N mutation was identified in one SCN1A-negative female patient with Dravet syndrome and a known PCDH19 p.N340S mutation in a female non-Dravet syndrome patient. The former also inherited a TSPYL4 p.G60R variant.
  
  
  CONCLUSIONS
  A high percentage of SCN1A mutations was identified in our Chinese cohort of Dravet syndrome patients but none in the rest of patients. We demonstrated that truncating/splice site mutations were linked to moderate to severe intellectual disability in these patients. A de novo PCDH19 missense mutation together with an inherited TSPYL4 missense variant were identified in a patient with Dravet syndrome.
authors: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors: Anna Ka-Yee
authors: AK
authors: Kwong
authors: Cheuk-Wing
authors: CW
authors: Fung
authors: Siu-Yuen
authors: SY
authors: Chan
authors: Virginia Chun-Nei
authors: VC
authors: Wong
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D015820:Cadherins / Q000737:chemistry / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000150:complications; D008297:Male; D009154:Mutation; D020125:Mutation, Missense / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000737:chemistry / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D000091363:Protocadherins; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: D015820:Cadherins; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009687:Nuclear Proteins; C438605:PCDH19 protein, human; D000091363:Protocadherins; D022821:RNA Splice Sites; C568242:SCN1A protein, human