Mutations in HPCA cause autosomal-recessive primary isolated dystonia.
Am J Hum Genet
; 96(4): 657-65, 2015 Apr 02.
Article
en En
| MEDLINE
| ID: mdl-25799108
ABSTRACT
Reports of primary isolated dystonia inherited in an autosomal-recessive (AR) manner, often lumped together as "DYT2 dystonia," have appeared in the scientific literature for several decades, but no genetic cause has been identified to date. Using a combination of homozygosity mapping and whole-exome sequencing in a consanguineous kindred affected by AR isolated dystonia, we identified homozygous mutations in HPCA, a gene encoding a neuronal calcium sensor protein found almost exclusively in the brain and at particularly high levels in the striatum, as the cause of disease in this family. Subsequently, compound-heterozygous mutations in HPCA were also identified in a second independent kindred affected by AR isolated dystonia. Functional studies suggest that hippocalcin might play a role in regulating voltage-dependent calcium channels. The identification of mutations in HPCA as a cause of AR primary isolated dystonia paves the way for further studies to assess whether "DYT2 dystonia" is a genetically homogeneous condition or not.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Distonía
/
Hipocalcina
/
Genes Recesivos
/
Mutación
Límite:
Humans
Idioma:
En
Revista:
Am J Hum Genet
Año:
2015
Tipo del documento:
Article
País de afiliación:
Reino Unido