MACHADO-JOSEPH-DISEASE MAPS TO THE SAME REGION OF CHROMOSOME-14 AS THE SPINOCEREBELLAR ATAXIA TYPE-3 LOCUS

Machado Joseph disease (MJD) is an autosomal dominantly inherited neur odegenerative disorder primarily affecting the motor system. It can be divided into three phenotypes based on the variable combination of a range of clinical symptoms including pyramidal and extrapyramidal feat ures, cerebellar deficits, and distal muscle atrophy. MJD is thought t o be caused by mutation of a single gene which has recently been mappe d, using genetic Linkage analysis, to a 29 cM region on chromosome 14q 24.3-q32 in five Japanese families. A second disorder, spino-cerebella r ataxia type 3 (SCA3), which has clinical symptoms similar to MJD, ha s also been linked to the same region of chromosome 14q in two French families. In order to narrow down the region of chromosome 14 which co ntains the MJD locus and to determine if this region overlaps with the predisposing locus for SCA3, we have performed genetic linkage analys is in seven MJD families, six of Portuguese/Azorean origin and one of Brazilian origin, using nine microsatellite markers mapped to 14q24.3- q32. Our results localise the MJD locus in these families to an 11 cM interval flanked by the markers D14S68 and AFM343vfl. In addition we s how that this 11 cM interval maps within the 15 cM interval containing the SCA3 locus, suggesting that these diseases are allelic.