title: High mutation rate in dopa-responsive dystonia: detection with comprehensive GCHI screening.
abstract: Mutations in GTP cyclohydrolase I (GCHI) are found in 50 to 60% of cases with dopa-responsive dystonia (DRD). Heterozygous GCHI exon deletions, undetectable by sequencing, have recently been described in three DRD families. We tested 23 individuals with DRD for the different mutation types by conventional and quantitative PCR analyses and found mutations, including two large exon deletions, in 87%. The authors attribute this high mutation rate to rigorous inclusion criteria and comprehensive mutational analysis.
authors.affiliation: Department of Neurology, University of Lübeck, Lübeck, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hagenah
authors.forename: R
authors.initials: R
authors.lastname: Saunders-Pullman
authors.forename: K
authors.initials: K
authors.lastname: Hedrich
authors.forename: K
authors.initials: K
authors.lastname: Kabakci
authors.forename: K
authors.initials: K
authors.lastname: Habermann
authors.forename: K
authors.initials: K
authors.lastname: Wiegers
authors.forename: K
authors.initials: K
authors.lastname: Mohrmann
authors.forename: T
authors.initials: T
authors.lastname: Lohnau
authors.forename: D
authors.initials: D
authors.lastname: Raymond
authors.forename: P
authors.initials: P
authors.lastname: Vieregge
authors.forename: T
authors.initials: T
authors.lastname: Nygaard
authors.forename: L J
authors.initials: LJ
authors.lastname: Ozelius
authors.forename: S B
authors.initials: SB
authors.lastname: Bressman
authors.forename: C
authors.initials: C
authors.lastname: Klein
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D004252:DNA Mutational Analysis; D004295:Dihydroxyphenylalanine / Q000494:pharmacology / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use; D004421:Dystonia / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests
chemical_list: D015259:Dopamine Agents; D004295:Dihydroxyphenylalanine; D006136:GTP Cyclohydrolase; D004298:Dopamine