Molecular mechanisms of hereditary progressive dystonia with marked diurnal fluctuation, Segawa's disease

The causative gene for hereditary progressive dystonia with marked diurnal fluctuation/dopa-responsive dystonia (HPD/DRD) was discovered in 1994 to be guanosine triphosphate (GTP) cyclohydrolase I, an enzyme involved in tetra hydrobiopterin biosynthesis. To the present, more than 50 mutations have be en found in this gene in HPD/DRD patients. Although it is clear that HPD/DR D is caused by partial deficiency of tetrahydrobiopterin in the brain, seve ral important issues regarding the molecular etiology of HPD/DRD remain to be addressed. We review herein the recent progress in the molecular genetic s of HPD/DRD and clarify the points to be answered. (C) 2000 Elsevier Scien ce B.V. All rights reserved.