Here we develop a mouse model carrying a human GNAO1 mutation (G203R) and determine whether the clinical features of patients with this GNAO1 mutation, which includes both epilepsy and movement disorder, would be evident in the mouse model.
<b>Expert opinion</b>: After secondary paroxysmal dyskinesias, the most common paroxysmal movement disorders are likely to be PRRT2-associated paroxysmal kinesigenic dyskinesias, which respond well to small doses of carbamazepine, and episodic ataxia type 2, which often responds to acetazolamide.
A focal motor seizure phenomenologically manifested as a defined movement disorder in 29% of the patients from a consecutive video-EEG documented cohort as per consensus among experts: myoclonus and dystonia (10 and 9 cases, respectively) were the most common movement disorders, followed by chorea (4), stereotypies (3) myoclonus-dystonia (2), and tremor (1).
Here we review a mechanistic model in which loss-of-function (LOF) GNAO1 alleles cause epilepsy and gain-of-function (GOF) alleles are primarily associated with movement disorders.
The authors report 2 cases of brothers with a severe movement disorder and hypotonia without epilepsy who have been confirmed by whole exome sequencing to have a novel mutation in GNAO1.
The authors report 2 cases of brothers with a severe movement disorder and hypotonia without epilepsy who have been confirmed by whole exome sequencing to have a novel mutation in GNAO1.
We hypothesize a pathogenic role of PRRT2 mutation in inducing benign myoclonus of early infancy, similarly to that at the origin of other PRRT2-related paroxysmal movement disorders, such as paroxysmal kinesigenic dyskinesia.
The authors report 2 cases of brothers with a severe movement disorder and hypotonia without epilepsy who have been confirmed by whole exome sequencing to have a novel mutation in GNAO1.