Clinical similarities of hereditary progressive/dopa responsivedystonia caused by different types of mutations in the GTPcyclohydrolase I gene

OBJECTIVE—Hereditary progressive dystonia withpronounced diurnal fluctuation ((HPD)/dopa responsive dystonia (DRD))is a childhood onset dystonia which responds to levodopa. Variousclinical signs and symptoms of HPD/DRD have been recognised to date.Mutations in the GTP cyclohydrolase I (GTP-CH-I) gene were recentlyidentified as the cause of HPD/DRD. In the present study, the GTP-CH-Igene and the clinical features of eight HPD/DRD patients from sixfamilies were analysed to determine the correlationsbetween clinical expression and the mutations in the GTP-CH-I gene.
METHODS—The exons, exon-intron junctions, and anindispensable part of the 5' flanking region of the GTP-CH-I gene weresequenced in the eight clinically diagnosed patients with HPD/DRD andtheir asymptomatic parents.
RESULTS—Three independent mutations in theGTP-CH-I gene were found in three patients. One of the patients and herasymptomatic mother were heterozygous for a novel mutation at theinitiation codon. The three patients with dissimilar GTP-CH-I mutationsexhibited similar clinical features. The other five patients withnormal sequences presented several features not manifested by the three patients with the mutations. No mutation was found in the 5' flanking region of any patients or their parents.
CONCLUSIONS—A novel initiation codon mutation wasfound in a Japanese patient with HPD/DRD. The clinical manifestationscommon to the patients with HPD/DRD with a mutated GTP-CH-I gene werealso identified. Although focal manifestations of HPD/DRD associatedwith the mutations of this gene will be broadened, it is inferred thatthese clinical features are fundamental to HPD/DRD caused by mutationsin this gene.