title: Mutations in the cyclic adenosine monophosphate response element of the tyrosine hydroxylase gene.
abstract: Tyrosine hydroxylase (TH) deficiency (OMIM 191290) is one cause of early-onset dopa-responsive dystonia. We describe seven cases from five unrelated families with dopa-responsive dystonia and low homovanillic acid in cerebrospinal fluid who were suspected to suffer from TH deficiency. Analysis of part of the TH promotor showed five homozygous and two heterozygous mutations in the highly conserved cyclic adenosine monophosphate response element. Our data suggest that, if no mutations are found in the coding regions of the gene in patients strongly suspected of TH deficiency, the search for pathogenic mutations should be extended to regulatory promotor elements.
authors: Department of Neurology and Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.verbeek@cukz.umcn.nl
authors: Marcel M
authors: MM
authors: Verbeek
authors: Gerry C H
authors: GC
authors: Steenbergen-Spanjers
authors: Michèl A A P
authors: MA
authors: Willemsen
authors: Frans A
authors: FA
authors: Hol
authors: Jan
authors: J
authors: Smeitink
authors: Jürgen
authors: J
authors: Seeger
authors: Padraic
authors: P
authors: Grattan-Smith
authors: Monique M
authors: MM
authors: Ryan
authors: Georg F
authors: GF
authors: Hoffmann
authors: Maria A
authors: MA
authors: Donati
authors: Nenad
authors: N
authors: Blau
authors: Ronald A
authors: RA
authors: Wevers
mesh_terms: D002648:Child; D002675:Child, Preschool; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004421:Dystonia / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D014446:Tyrosine 3-Monooxygenase