SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy.

ABSTRACT: Essential tremor (ET) is the most prevalent movement disorder, affecting millions of people in the USA. Although a positive family history is one of the most important risk factors for ET, the genetic causes of ET remain unknown. In an attempt to identify genetic causes for ET, we performed whole-exome sequencing analyses in a large Spanish family with ET, in which two patients also developed epilepsy. To further assess pathogenicity, site-directed mutagenesis, mouse and human brain expression analyses, and patch clamp techniques were performed. A disease-segregating mutation (p.Gly1537Ser) in the SCN4A gene was identified. Posterior functional analyses demonstrated that more rapid kinetics at near-threshold potentials altered ion selectivity and facilitated the conductance of both potassi

SUBMITTER: Bergareche A 

PROVIDER: S-EPMC4654061 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature