MACHADO-JOSEPH-DISEASE IN 3 SCANDINAVIAN FAMILIES

Machado-Joseph disease (MJD) is an autosomal dominantly inherited neur odegenerative disorder characterized by varying age of onset and prono unced phenotypic heterogeneity. The clinical core features include gai t ataxia, external ophthalmoplegia, nystagmus, and bulging eyes. Recen tly, Kawagushi el al. (1994) cloned the MJD1 gene on chromosome 14 and MJD turned out to be the fifth neurodegenerative disease caused by an unstable CAG repeat expansion. Pie have studied two large Danish fami lies and one Norwegian family with MJD. Three features not previously associated with MJD are reported: dementia, generalized muscle and joi nt pain, and in one case neuropathological examination revealed atroph y of the inferior olives. We found a significant inverse correlation b etween age of onset and the length of the CAG repent expansion, and an ticipation is described through four succeeding generations. Instabili ty of the CAG repeat expansion was mast pronounced at paternal transmi ssion. (C) 1998 Elsevier Science B.V.