Short communicationComplex SCN8A DNA-abnormalities in an individual with therapy resistant absence epilepsy

•We identified a deletion of exons 2-14 of SCN8A in an epileptic encephalopathy case.•The deletion turned out to be mosaic.•The patient also carries a SCN8A variant on the other allele and a SCN5A variant.•We discuss loss of function of SCN8A as mechanism in causing epilepsy.•We discuss the possible role of genetic modifiers and cellular interference.

BackgroundDe novo SCN8A missense mutations have been identified as a rare dominant cause of epileptic encephalopathy. We described a person with epileptic encephalopathy associated with a mosaic deletion of the SCN8A gene.MethodsArray comparative genome hybridization was used to identify chromosomal abnormalities. Next Generation Sequencing was used to screen for variants in known and candidate epilepsy genes. A single nucleotide polymorphism array was used to test whether the SCN8A variants were in cis or in trans.ResultsWe identified a de novo mosaic deletion of exons 2-14 of SCN8A, and a rare maternally inherited missense variant on the other allele in a woman presenting with absence seizures, challenging behavior, intellectual disability and QRS-fragmentation on the ECG. We also found a variant in SCN5A.ConclusionsThe combination of a rare missense variant with a de novo mosaic deletion of a large part of the SCN8A gene suggests that other possible mechanisms for SCN8A mutations may cause epilepsy; loss of function, genetic modifiers and cellular interference may play a role. This case expands the phenotype associated with SCN8A mutations, with absence epilepsy and regression in language and memory skills.