PubMed 26220391

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Automatically associated channels: Nav1.5 , Nav1.6

Title: Complex SCN8A DNA-abnormalities in an individual with therapy resistant absence epilepsy.

Authors: Bianca Berghuis, Carolien G F de Kovel, Loretta van Iterson, Robert J Lamberts, Josemir W Sander, Dick Lindhout, Bobby P C Koeleman

Journal, date & volume: Epilepsy Res., 2015 Sep , 115, 141-4

PubMed link:

De 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.Array 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.We 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.The 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.