AUTHOR=Wagnon Jacy L. , Meisler Miriam H. 

TITLE=Recurrent and Non-Recurrent Mutations of SCN8A in Epileptic Encephalopathy

JOURNAL=Frontiers in Neurology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2015.00104

DOI=10.3389/fneur.2015.00104

ISSN=1664-2295

ABSTRACT=<p>Mutations of the voltage-gated sodium channel <italic>SCN8A</italic> have been identified in approximately 1% of nearly 1,500 children with early-infantile epileptic encephalopathies (EIEE) who have been tested by DNA sequencing. EIEE caused by mutation of <italic>SCN8A</italic> is designated EIEE13 (OMIM #614558). Affected children have seizure onset before 18 months of age as well as developmental and cognitive disabilities, movement disorders, and a high incidence of sudden death (SUDEP). EIEE13 is caused by <italic>de novo</italic> missense mutations of evolutionarily conserved residues in the Na<sub>v</sub>1.6 channel protein. One-third of the mutations are recurrent, and many occur at CpG dinucleotides. In this review, we discuss the effect of pathogenic mutations on the structure of the channel protein, the rate of recurrent mutation, and changes in channel function underlying this devastating disorder.</p>