Partial loss-of-function of sodium channel SCN8A in familial isolated myoclonus.

ABSTRACT: Variants in the neuronal sodium channel gene SCN8A have been implicated in several neurological disorders. Early infantile epileptic encephalopathy type 13 results from de novo gain-of-function mutations that alter the biophysical properties of the channel. Complete loss-of-function variants of SCN8A have been identified in cases of isolated intellectual disability. We now report a novel heterozygous SCN8A variant, p.Pro1719Arg, in a small pedigree with five family members affected with autosomal dominant upper limb isolated myoclonus without seizures or cognitive impairment. Functional analysis of the p.Pro1719Arg variant in transfected neuron-derived cells demonstrated greatly reduced Na_v 1.6 channel activity without altered gating properties. Hypomorphic alleles of Scn8a in t

SUBMITTER: Wagnon JL 

PROVIDER: S-EPMC6032947 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature