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.