Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene
- Yoshiko Tamarua,b,
- Makito Hiranoa,d,
- Hidefumi Itob,
- Junichiro Kawamurac,
- Sadayuki Matsumotob,
- Terukuni Imaib,
- Satoshi Uenoa
- aDepartment of Medical Genetics, Nara Medical University, Kashihara, Nara, 634, Japan, bDepartment of Neurology, Kitano Hospital and Neurological Center, Osaka, Japan, cDepartment of Neurology, Kobe City General Hospital, Kobe, Japan, dDepartment of Neurology, Osaka University Medical School, Osaka, Japan
- Dr Satoshi Ueno, Department of Medical Genetics, Nara Medical University, Kashihara, Nara, 634, Japan.
- Received 7 January 1997
- Revised 10 July 1997
- Accepted 21 August 1997
Abstract
OBJECTIVE Hereditary progressive dystonia with pronounced diurnal fluctuation ((HPD)/dopa responsive dystonia (DRD)) is a childhood onset dystonia which responds to levodopa. Various clinical signs and symptoms of HPD/DRD have been recognised to date. Mutations in the GTP cyclohydrolase I (GTP-CH-I) gene were recently identified as the cause of HPD/DRD. In the present study, the GTP-CH-I gene and the clinical features of eight HPD/DRD patients from six families were analysed to determine the correlations between clinical expression and the mutations in the GTP-CH-I gene.
METHODS The exons, exon-intron junctions, and an indispensable part of the 5’ flanking region of the GTP-CH-I gene were sequenced in the eight clinically diagnosed patients with HPD/DRD and their asymptomatic parents.
RESULTS Three independent mutations in the GTP-CH-I gene were found in three patients. One of the patients and her asymptomatic mother were heterozygous for a novel mutation at the initiation codon. The three patients with dissimilar GTP-CH-I mutations exhibited similar clinical features. The other five patients with normal 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 was found in a Japanese patient with HPD/DRD. The clinical manifestations common to the patients with HPD/DRD with a mutated GTP-CH-I gene were also identified. Although focal manifestations of HPD/DRD associated with the mutations of this gene will be broadened, it is inferred that these clinical features are fundamental to HPD/DRD caused by mutations in this gene.
