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.