Association of nonsense mutation in GABRG2 with abnormal trafficking of GABAA receptors in severe epilepsy

Ishii, Atsushi; Kanaumi, Takeshi; Sohda, Miwa; Misumi, Yoshio; Zhang, Bo; Kakinuma, Naoto; Haga, Yutaka; Watanabe, Kazuyoshi; Takeda, Sén; Okada, Motohiro; Ueno, Shinji; Kaneko, Sunao; Takashima, Sachio; Hirose, Shinichi

doi:10.1016/j.eplepsyres.2013.12.005

Cited by 40 publications

(33 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At present, Dravet syndrome is thought to result from two heterozygous nonsense mutations, Q40* and Q390* Ishii et al, 2014). A heterozygous nonsense mutation of GABRG2, Q40*, was identified in dizygotic twin girls whose phenotype was compatible with that of Dravet syndrome.…”

Section: Mutations In Dravet Syndromementioning

confidence: 99%

Mutant GABAA receptor subunits in genetic (idiopathic) epilepsy

Hirose

2014

Progress in Brain Research

Self Cite

140

View full text Add to dashboard Cite

Section: Mutations In Dravet Syndromementioning

confidence: 99%

Mutant GABAA receptor subunits in genetic (idiopathic) epilepsy

Hirose

2014

Progress in Brain Research

Self Cite

140

View full text Add to dashboard Cite

“…Mutations in the sodium channel-encoding gene SCN1A account for the majority of Dravet syndrome cases [6,7] and have also been found to cause milder forms of epilepsy, migraine, and autism without epilepsy [8][9][10]. Mutations in SCN1B [11], SCN2A [12], and GABRG2 [13] are also known causes of Dravet syndrome, with additional genes such as PCDH19 and CHD2 found to cause Dravet-like phenotypes when mutated [14,15]. The discovery of these genes represents a major scientific advance, making it possible to perform genetic testing of patients with suspected Dravet syndrome that leads to the identification and diagnosis of milder or clinically "atypical" Dravet syndrome cases [5,16].…”

Section: Introductionmentioning

confidence: 98%

The European patient with Dravet syndrome: Results from a parent-reported survey on antiepileptic drug use in the European population with Dravet syndrome

Aras¹,

Isla²,

Mingorance³

2015

Epilepsy & Behavior

View full text Add to dashboard Cite

Dravet syndrome is a rare form of epilepsy largely refractory to current antiepileptic medications. The only precedents of randomized placebo-controlled trials in Dravet syndrome are the two small trials that led to the approval of stiripentol. With the arrival of new clinical trials for Dravet syndrome, we sought to determine the characteristics of the patient population with Dravet syndrome in Europe today, which has possibly evolved subsequent to the approval of stiripentol and the ability to diagnose milder clinical cases via genetic testing. From May to June 2014, we conducted an online parent-reported survey to collect information about the demographics, disease-specific clinical characteristics, as well as current and past use of antiepileptic medications by European patients with Dravet syndrome. We present data from 274 patients with Dravet syndrome from 15 European countries. Most patients were between 4 and 8years of age, and 90% had known mutations in SCN1A. Their epilepsy was characterized by multiple seizure types, although only 45% had more than 4 tonic-clonic seizures per month on average. The most common drug combination was valproate, clobazam, and stiripentol, with 42% of the total population currently taking stiripentol. Over a third of patients with Dravet syndrome had taken sodium channel blockers in the past, and most had motor and behavioral comorbidities. Our study helps define the current typical European patient with Dravet syndrome. The results from this survey may have important implications for the design of future clinical trials that investigate new treatments for Dravet syndrome.

show abstract

“…Q40X is associated with twin sisters with Dravet syndrome 37;38,39 . R136X is associated with GEFS+ and other extended phenotypes like eye myoclonia and autistic features 40 .…”

Section: Introductionmentioning

confidence: 99%