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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.    Conclusion  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.

Identification of SCN1A and PCDH19 Mutations in Chinese Children with Dravet Syndrome