Guanosine triphosphate cyclohydrolase 1 promoter deletion causes dopa-responsive dystonia

Jessie Theuns, David Crosiers, Luc Debaene, Karen Nuytemans, Bram Meeus, Kristel Sleegers, Dirk Goossens, Ellen Corsmit, Ellen Elinck, Karin Peeters, Maria Mattheijssens, Barbara Pickut, Jurgen Del-Favero, Sebastiaan Engelborghs, Peter Paul De Deyn, Patrick Cras, Christine Van Broeckhoven

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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 and Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1451-1456
Number of pages6
JournalMovement Disorders
Issue number11
StatePublished - Sep 15 2012
Externally publishedYes


  • Copy number variant
  • Dopa-responsive dystonia
  • Genome-wide linkage analysis
  • Large deletion
  • Promoter

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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