Dopa-responsive dystonia due to a large deletion in the GTP cyclohydrolase I gene.
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.
Furukawa
Y
Y
Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada.
Guttman
M
M
Sparagana
S P
SP
Trugman
J M
JM
Hyland
K
K
Wyatt
P
P
Lang
A E
AE
Rouleau
G A
GA
Shimadzu
M
M
Kish
S J
SJ
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
D018076:DNA, Complementary; D015259:Dopamine Agents; D007980:Levodopa; D006136:GTP Cyclohydrolase