Guanosine triphosphate cyclohydrolase 1 promoter deletion causes dopa-responsive dystonia.
Mov Disord
; 27(11): 1451-6, 2012 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-22976901
ABSTRACT
BACKGROUND:
Autosomal dominant dopa-responsive dystonia (AD-DRD) is caused by a biochemical defect primarily resulting from guanosine triphosphate cyclohydrolase 1 gene (GCH1) mutations. Few families have been reported without mutations in GCH1.METHODS:
Genome-wide linkage analysis and positional cloning to identify the genetic defect in a Belgian AD-DRD family was carried out. RESULTS ANDCONCLUSION:
In this study, we report on the identification and characterization of a novel 24-kb deletion spanning exon 1 and the 5' regulatory region of GCH1 causing a wide spectrum of motor and nonmotor symptoms in a large Belgian AD-DRD family. This large-scale deletion of regulatory sequences leads to decreased GCH1 activity in all carriers, most probably resulting from allelic loss of transcription. We mapped the breakpoints of this deletion to the nucleotide level, allowing the development of a straightforward polymerase chain reaction assay for fast, efficient detection of this large deletion, which will prove valuable for preimplantation genetic diagnosis.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Regiões Promotoras Genéticas
/
Deleção de Sequência
/
Distonia
/
GTP Cicloidrolase
Tipo de estudo:
Etiology_studies
Limite:
Adult
/
Female
/
Humans
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Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Mov Disord
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Bélgica