Machado-Joseph Disease / Spinocerebellar Ataxia Type 3

Abstract

Machado-joseph disease (MJD) is a dominantly inherited ataxia, which was first described among immigrants from the portuguese azorean islands. Affected persons typically displayed progressive ataxia, often with parkinsonian features and motor neuron involvement. The clinical features of MJD sometimes varied greatly even within the same family. In the early 1990s, the genetic locus for MJD was narrowed to chromosome 14q, and the pathogenic mutation was soon discovered to be an unstable expansion of a GAG repeat in the MJDl gene. The pathogenic repeat encodes an expanded stretch of the amino acid glutamine in the disease protein, known as ataxin-3 or MJDlp. At the same time, the MJDl gene defect was being identified; European scientists separately mapped what had been thought to be an unrelated ataxia, spinocerebellar ataxia type 3 (SGA3), to the same chromosomal region. But once the pathogenic expansion underlying MJD was discovered it soon became clear that SGA3 was caused by the same mutation. Thus, MJD and SGA3 are the same genetic disorder. © 2006 Elsevier Inc. All rights reserved.