CLINICAL AND PATHOLOGICAL-STUDY OF A LARGE JAPANESE FAMILY WITH MACHADO-JOSEPH DISEASE TIGHTLY LINKED TO THE DNA MARKERS ON CHROMOSOME 14Q

The gene locus for Machado-Joseph disease (MJD) has been mapped to chr omosome 14q by linkage analysis, mainly using a single large Japanese family. We studied the clinical and neuropathologic findings of this f amily with MJD, comparing them with those of spinocerebellar ataxia 1 (SCA1) and spinocerebellar ataxia 2 (SCA2) families. The pedigree incl uded 30 affected persons in 125 members of five generations. Neurologi c examination of 21 patients revealed that dystonia, difficulty in eye lid opening, slowness of movements, bulging eyes, and facial-lingual f asciculation-like movements or myokymia are characteristic of this MJD family, although these three autosomal dominant spinocerebellar degen erations have several neurologic signs and symptoms in common. In cont rast with SCAI and SCA2, degeneration of the subthalamopallidal system and relative sparing of the olivocerebellar system were the main neur opathologic features of MJD.