Exome sequencing identifies FUS mutations as a cause of essential tremor.
Am J Hum Genet
; 91(2): 313-9, 2012 Aug 10.
Article
em En
| MEDLINE
| ID: mdl-22863194
ABSTRACT
Essential tremor (ET) is a common neurodegenerative disorder that is characterized by a postural or motion tremor. Despite a strong genetic basis, a gene with rare pathogenic mutations that cause ET has not yet been reported. We used exome sequencing to implement a simple approach to control for misdiagnosis of ET, as well as phenocopies involving sporadic and senile ET cases. We studied a large ET-affected family and identified a FUS p.Gln290(∗) mutation as the cause of ET in this family. Further screening of 270 ET cases identified two additional rare missense FUS variants. Functional considerations suggest that the pathogenic effects of ET-specific FUS mutations are different from the effects observed when FUS is mutated in amyotrophic lateral sclerosis cases; we have shown that the ET FUS nonsense mutation is degraded by the nonsense-mediated-decay pathway, whereas amyotrophic lateral sclerosis FUS mutant transcripts are not.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
/
Tremor Essencial
/
Proteína FUS de Ligação a RNA
/
Exoma
Tipo de estudo:
Prognostic_studies
Limite:
Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Am J Hum Genet
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Canadá