Confirming the recessive inheritance of SCN1B mutations in developmental epileptic encephalopathy

Abstract

Dominant SCN1B mutations are known to cause several epilepsy syndromes in humans. Only 2 epilepsy patients to date have been reported to have recessive mutations in SCN1B as the likely cause of their phenotype. Here, we confirm the recessive inheritance of 2 novel SCN1B mutations in 5 children from 3 families with developmental epileptic encephalopathy. The recessive inheritance and early death in these patients is consistent with the Dravet-like phenotype observed in Scn1b^-/- mice. The 'negative' clinical exome in one of these families highlights the need to consider recessive mutations in the interpretation of variants in typically dominant genes.

Keywords: SCN1B; GEFS+; clinical exome; epilepsy; haploinsufficiency; homozygous mutation; voltage-gated sodium channel.