[ML-4] A Story of Identification of the Causative Gene for Segawa’s Disease.
It was the evening on a day at the end of December in 1993. I was just going back to my home, and passed by Prof. Toshiharu Nagatsu, who was reading a December issue of Nature Genetics. He said to me, “The chromosomal locus for dopa-responsive dystonia was mapped to chromosome 14q”. I read the paper by Dr. Nygaard et al. and learned that L-dopa was very effective to the disease and that the neopterin and biopterin levels in the CSF of the patients were markedly reduced. One idea hit me that GTP cyclohydrolase I, the rate-limiting enzyme for biosynthesis of biopterin, might be the causative gene for dopa-responsive dystonia, because we were mapping the chromosome locus of GTP cyclohydrolase I in collaboration with Dr. Tada-aki Hori to be 14q22.1-q22.2. Then, I told my idea to Prof. Nagatsu and he discussed it with late Prof. Yoshida (He was a professor of neurology at Jichi Medical School at the time). Prof. Yoshida taught us that dopa-responsive dystonia is likely to be the same with Segawa’s disease, and he kindly arranged the collaboration with Dr. Segawa. Then, the project started. Dr. Segawa and Dr. Nomura provided us with some patients’ blood. However, it was not a straight way because the heritage of the disease was a dominant trait and it was unusual that a heterozygous mutation of an enzyme cause dominantly inherited disorders. Thanks to many collaborators, we finally succeeded in identification of the causative gene for Segawa’s disease.