Mutations in ANO3 cause dominant craniocervical dystonia: ion channel implicated in pathogenesis.
Am J Hum Genet
; 91(6): 1041-50, 2012 Dec 07.
Article
en En
| MEDLINE
| ID: mdl-23200863
ABSTRACT
In this study, we combined linkage analysis with whole-exome sequencing of two individuals to identify candidate causal variants in a moderately-sized UK kindred exhibiting autosomal-dominant inheritance of craniocervical dystonia. Subsequent screening of these candidate causal variants in a large number of familial and sporadic cases of cervical dystonia led to the identification of a total of six putatively pathogenic mutations in ANO3, a gene encoding a predicted Ca(2+)-gated chloride channel that we show to be highly expressed in the striatum. Functional studies using Ca(2+) imaging in case and control fibroblasts demonstrated clear abnormalities in endoplasmic-reticulum-dependent Ca(2+) signaling. We conclude that mutations in ANO3 are a cause of autosomal-dominant craniocervical dystonia. The locus DYT23 has been reserved as a synonym for this gene. The implication of an ion channel in the pathogenesis of dystonia provides insights into an alternative mechanism that opens fresh avenues for further research.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tortícolis
/
Canales de Cloruro
/
Genes Dominantes
/
Mutación
Tipo de estudio:
Etiology_studies
Límite:
Female
/
Humans
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Male
Idioma:
En
Revista:
Am J Hum Genet
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido