BACKGROUND: Dravet syndrome is a severe infantile epileptic encephalopathy 
caused in approximately 80% of cases by mutations in the voltage gated sodium 
channel subunit gene SCN1A. The majority of these mutations are de novo. The 
parental origin of de novo mutations varies widely among genetic disorders and 
the aim of this study was to determine this for Dravet syndrome.
METHODS: 91 patients with de novo SCN1A mutations and their parents were 
genotyped for single nucleotide polymorphisms (SNPs) in the region surrounding 
their mutation. Allele specific polymerase chain reaction (PCR) based on 
informative SNPs was used to separately amplify and sequence the paternal and 
maternal alleles to determine in which parental chromosome the mutation arose.
RESULTS: The parental origin of SCN1A mutations was established in 44 patients 
for whom both parents were available and SNPs were informative. The mutations 
were of paternal origin in 33 cases and of maternal origin in the remaining 11 
cases. De novo mutation of SCN1A most commonly, but not exclusively, originates 
from the paternal chromosome. The average age of parents originating mutations 
did not differ from that of the general population.
CONCLUSIONS: The greater frequency of paternally derived mutations in SCN1A is 
likely to be due to the greater chance of mutational events during the increased 
number of mitoses which occur during spermatogenesis compared to oogenesis, and 
the greater susceptibility to mutagenesis of the methylated DNA characteristic 
of sperm cells.