HEREDITARY PROGRESSIVE DYSTONIA WITH MARKED DIURNAL FLUCTUATION CAUSED BY MUTATIONS IN THE GTP CYCLOHYDROLASE-I GENE

Hereditary progressive dystonia with marked diurnal fluctuation (HPD) (also known as dopa responsive dystonia) is a dystonia with onset in c hildhood that shows a marked response without any side effects to levo dopa. Recently the gene for dopa responsive dystonia (DRD) was mapped to chromosome 14q. Here we report that GTP cyclohydrolase I is mapped to 14q22.1-q22.2. The identification of four independent mutations of the gene for GTP cyclohydrolase I in patients with HPD, as well as a m arked decrease in the enzymes activity in mononuclear blood cells, con firms that the GTP cyclohydrolase I gene is a causative gene for HPD/D RD. This is the first report of a causative gene for the inherited dys tonias.