[Identification of the causative gene for Segawa's disease]

In 1994, we identified the GTP cyclohydrolase I (GCH) gene, an enzyme for biosynthesis of tetrahydrobiopterin, as the causative gene for Segawa's disease. On the way of our research, both biochemical and molecular biological approaches were essential. We could measure biopterin and the GCH activity, since we had worked on catecholamine- and biopterin-synthesizing enzymes for many years. The measurements of the GCH activity in mononuclear blood cells made us confident that GCH could be a causative gene for the disease, while the chromosomal locus of the GCH gene was the beginning of the idea. The research was greatly accelerated by efficient collaboration among many researchers including Dr. Segawa, and we deeply appreciate their collaboration. Although the causative gene for Segawa's disease had been identified, there remain several important issues to be addressed. Presence of asymptomatic carriers, who have the same mutation in the GCH gene as the patients, suggests involvement of other factors for development of symptoms. The factors shall be associated with a female-predominance of the disease.