title: Guanosine triphosphate cyclohydrolase 1 promoter deletion causes dopa-responsive dystonia.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium. jessie.theuns@molgen.vib-ua.be
authors.forename: Jessie
authors.initials: J
authors.lastname: Theuns
authors.forename: David
authors.initials: D
authors.lastname: Crosiers
authors.forename: Luc
authors.initials: L
authors.lastname: Debaene
authors.forename: Karen
authors.initials: K
authors.lastname: Nuytemans
authors.forename: Bram
authors.initials: B
authors.lastname: Meeus
authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.forename: Dirk
authors.initials: D
authors.lastname: Goossens
authors.forename: Ellen
authors.initials: E
authors.lastname: Corsmit
authors.forename: Ellen
authors.initials: E
authors.lastname: Elinck
authors.forename: Karin
authors.initials: K
authors.lastname: Peeters
authors.forename: Maria
authors.initials: M
authors.lastname: Mattheijssens
authors.forename: Barbara
authors.initials: B
authors.lastname: Pickut
authors.forename: Jurgen
authors.initials: J
authors.lastname: Del-Favero
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: De Deyn
authors.forename: Patrick
authors.initials: P
authors.lastname: Cras
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
mesh_terms: D000328:Adult; D001530:Belgium; D002874:Chromosome Mapping; D015259:Dopamine Agents / Q000627:therapeutic use; D004421:Dystonia / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D055815:Young Adult
chemical_list: D015259:Dopamine Agents; D007980:Levodopa; D006136:GTP Cyclohydrolase