抄録
Paroxysmal dystonic choreoathetosis (PDC) is thought to be a hereditary channelopathy mapped to chromosome 2q32-36. By means of linkage analysis on a large Japanese family, we have narrowed the PDC locus that contains 32 candidate genes. Here, we report that a heterozygous mutation (A7V) in one of such genes, myofibrillogenesis regulator 1 (MR-1), is responsible for PDC in the Japanese family. This is consistent with the finding in American PDC families. We further report that there are several other polymorphisms in MR-1 in the Japanese PDC family. To characterize MR-1, we generated specific antibodies against MR-1 and performed the immunohistochemical analysis in rat brain. The results of the MR-1 localization will be discussed. Similar to other channelopathies such as epilepsy and migraine, PDC is characterized by involuntary movement attacks, and is presumed to be induced by abnormalities of ion channels. Although MR-1 may be associated with some ion channels, its physiological functions remain unclear. Further characterization of MR-1 including its molecular function and relationship to ion channels, may facilitate not only to understand pathophysiology of PDC, but also to develop effective therapies for paroxysmal neurological disorders. [J Physiol Sci. 2006;56 Suppl:S157]
