Movement disorder in GNAO1 encephalopathy associated with gain-of-function mutations.

ABSTRACT:

Objective

To define molecular mechanisms underlying the clinical spectrum of epilepsy and movement disorder in individuals with de novo mutations in the GNAO1 gene.

Methods

We identified all GNAO1 mutations reported in individuals with epilepsy (early infantile epileptiform encephalopathy 17) or movement disorders through April 2016; 15 de novo mutant alleles from 25 individuals were introduced into the Gα_o subunit by site-directed mutagenesis in a mammalian expression plasmid. We assessed protein expression and function in vitro in HEK-293T cells by Western blot and determined functional Gα_o-dependent cyclic adenosine monophosphate (cAMP) inhibition with a coexpressed α_2A adrenergic receptor.

Results

Of the 15 clinical <

SUBMITTER: Feng H 

PROVIDER: S-EPMC5580866 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature