P. Stgeorgehyslop et al., MACHADO-JOSEPH-DISEASE IN PEDIGREES OF AZOREAN DESCENT IS LINKED TO CHROMOSOME-14, American journal of human genetics, 55(1), 1994, pp. 120-125
A locus for Machado-Joseph disease (MJD) has recently been mapped to a
30-cM region of chromosome 14q in five pedigrees of Japanese descent.
MJD is a clinically pleomorphic neurodegenerative disease that was or
iginally described in subjects of Azorean descent. In light of the non
allelic heterogeneity in other inherited spinocerebellar ataxias, we w
ere interested to determine if the MJD phenotype in Japanese and Azore
an pedigrees arose from mutations at the same locus. We provide eviden
ce that MJD in five pedigrees of Azorean descent is also linked to chr
omosome 14q in an 18-cM region between the markers D14S67 and AACT (mu
ltipoint lod score +7.00 near D14S81). We also report molecular eviden
ce for homozygosity at the MJD locus in an MJD-affected subject with s
evere, early-onset symptoms. These observations confirm the initial re
port of linkage of MJD to chromosome 14; suggest that MJD in Japanese
and Azorean subjects may represent allelic or identical mutations at t
he same locus; and provide one possible explanation (MJD gene dosage)
for the observed phenotypic heterogeneity in this disease.