title: Dopa-responsive dystonia due to a large deletion in the GTP cyclohydrolase I gene.
abstract: Although it is assumed that most patients with autosomal dominant dopa-responsive dystonia (DRD) have a GTP cyclohydrolase I dysfunction, conventional genomic DNA sequencing of the gene (GCH1) coding for this enzyme fails to reveal any mutations in about 40% of DRD patients, which makes molecular genetic diagnosis difficult. We found a large heterozygous GCH1 deletion, which cannot be detected by the usual genomic DNA sequence analysis, in a three-generation DRD family and conclude that a large genomic deletion in GCH1 may account for some "mutation-negative" patients with dominantly inherited DRD.
authors.affiliation: Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Furukawa
authors.forename: M
authors.initials: M
authors.lastname: Guttman
authors.forename: S P
authors.initials: SP
authors.lastname: Sparagana
authors.forename: J M
authors.initials: JM
authors.lastname: Trugman
authors.forename: K
authors.initials: K
authors.lastname: Hyland
authors.forename: P
authors.initials: P
authors.lastname: Wyatt
authors.forename: A E
authors.initials: AE
authors.lastname: Lang
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: M
authors.initials: M
authors.lastname: Shimadzu
authors.forename: S J
authors.initials: SJ
authors.lastname: Kish
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D015259:Dopamine Agents / Q000008:administration & dosage; D004421:Dystonia / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D005192:Family Health; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D018076:DNA, Complementary; D015259:Dopamine Agents; D007980:Levodopa; D006136:GTP Cyclohydrolase