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 journalArticle

9 Citations (Scopus)

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 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
Volume27
Issue number11
DOIs
StatePublished - Sep 15 2012
Externally publishedYes

Fingerprint

Guanosine Triphosphate
Genes
Preimplantation Diagnosis
Mutation
Sequence Deletion
Loss of Heterozygosity
Nucleic Acid Regulatory Sequences
Organism Cloning
Exons
Nucleotides
Genome
Polymerase Chain Reaction
Dopa-Responsive Dystonia

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Theuns, J., Crosiers, D., Debaene, L., Nuytemans, K., Meeus, B., Sleegers, K., ... Van Broeckhoven, C. (2012). Guanosine triphosphate cyclohydrolase 1 promoter deletion causes dopa-responsive dystonia. Movement Disorders, 27(11), 1451-1456. https://doi.org/10.1002/mds.25147

Guanosine triphosphate cyclohydrolase 1 promoter deletion causes dopa-responsive dystonia. / Theuns, Jessie; Crosiers, David; Debaene, Luc; Nuytemans, Karen; Meeus, Bram; Sleegers, Kristel; Goossens, Dirk; Corsmit, Ellen; Elinck, Ellen; Peeters, Karin; Mattheijssens, Maria; Pickut, Barbara; Del-Favero, Jurgen; Engelborghs, Sebastiaan; De Deyn, Peter Paul; Cras, Patrick; Van Broeckhoven, Christine.

In: Movement Disorders, Vol. 27, No. 11, 15.09.2012, p. 1451-1456.

Research output: Contribution to journalArticle

Theuns, J, Crosiers, D, Debaene, L, Nuytemans, K, Meeus, B, Sleegers, K, Goossens, D, Corsmit, E, Elinck, E, Peeters, K, Mattheijssens, M, Pickut, B, Del-Favero, J, Engelborghs, S, De Deyn, PP, Cras, P & Van Broeckhoven, C 2012, 'Guanosine triphosphate cyclohydrolase 1 promoter deletion causes dopa-responsive dystonia', Movement Disorders, vol. 27, no. 11, pp. 1451-1456. https://doi.org/10.1002/mds.25147
Theuns, Jessie ; Crosiers, David ; Debaene, Luc ; Nuytemans, Karen ; Meeus, Bram ; Sleegers, Kristel ; Goossens, Dirk ; Corsmit, Ellen ; Elinck, Ellen ; Peeters, Karin ; Mattheijssens, Maria ; Pickut, Barbara ; Del-Favero, Jurgen ; Engelborghs, Sebastiaan ; De Deyn, Peter Paul ; Cras, Patrick ; Van Broeckhoven, Christine. / Guanosine triphosphate cyclohydrolase 1 promoter deletion causes dopa-responsive dystonia. In: Movement Disorders. 2012 ; Vol. 27, No. 11. pp. 1451-1456.
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