STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern.
Epilepsia
; 51(12): 2397-405, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-20887364
ABSTRACT
PURPOSE:
De novo STXBP1 mutations have been found in individuals with early infantile epileptic encephalopathy with suppression-burst pattern (EIEE). Our aim was to delineate the clinical spectrum of subjects with STXBP1 mutations, and to examine their biologic aspects.METHODS:
STXBP1 was analyzed in 29 and 54 cases of cryptogenic EIEE and West syndrome, respectively, as a second cohort. RNA splicing was analyzed in lymphoblastoid cells from a subject harboring a c.663 + 5G>A mutation. Expression of STXBP1 protein with missense mutations was examined in neuroblastoma2A cells.RESULTS:
A total of seven novel STXBP1 mutations were found in nine EIEE cases, but not in West syndrome. The mutations include two frameshift mutations, three nonsense mutations, a splicing mutation, and a recurrent missense mutation in three unrelated cases. Including our previous data, 10 of 14 individuals (71%) with STXBP1 aberrations had the onset of spasms after 1 month, suggesting relatively later onset of epileptic spasms. Nonsense-mediated mRNA decay associated with abnormal splicing was demonstrated. Transient expression revealed that STXBP1 proteins with missense mutations resulted in degradation in neuroblastoma2A cells.DISCUSSION:
Collectively, STXBP1 aberrations can account for about one-third individuals with EIEE (14 of 43). These genetic and biologic data clearly showed that haploinsufficiency of STXBP1 is the important cause for cryptogenic EIEE.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espasmos Infantis
/
Epilepsia Generalizada
/
Mutação de Sentido Incorreto
/
Eletroencefalografia
/
Proteínas Munc18
/
Haploinsuficiência
Tipo de estudo:
Diagnostic_studies
Limite:
Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Epilepsia
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Japão