Bw. Soong et al., MACHADO-JOSEPH-DISEASE - CLINICAL, MOLECULAR, AND METABOLIC CHARACTERIZATION IN CHINESE KINDREDS, Annals of neurology, 41(4), 1997, pp. 446-452
Machado-Joseph disease, an autosomal dominant multisystem motor degene
ration, has been described mainly in people of Portuguese descent. Our
report documents the presence of Machado-Joseph disease in the Chines
e population, based on the specific molecular marker of a CAG repeat a
rray in the 3' end of the MJD gene. We screened 21 Chinese families wi
th dominant spinocerebellar ataxia. The results showed that Machado-Jo
seph disease with GAG expansion accounted for 52% of families with aut
osomal dominant cerebellar ataxia in this series. The clinical charact
eristics, besides the well-documented cerebellar ataxia, dysarthria, n
ystagmus, corticospinal dysfunctions, a variable degree of facial musc
le fasciculation, and proprioceptive loss, included loss of optokineti
c nystagmus and autonomic nervous system dysfunction, The CAG repeat n
umber in the MJD gene ranged from 14 to 39 among normal alleles, and f
rom 63 to 81 among MJD alleles. There was a strong inverse correlation
(gamma = -0.77) between number of CAG repeats and age at symptom onse
t, accounting for 60% of the variance of age at onset. A strong clinic
al anticipation of age at onset existed in successive generations. Mil
d instabilities of expanded CAG repeat numbers during meiotic transmis
sion occurred, with no significant difference according to the gender
of the transmitting parent. Finally, brain metabolism in Machado-Josep
h disease, studied with positron emission tomography, was characterize
d by significant progressive regional hypometabolism in the occipital
cortex, as well as the cerebellar hemispheres, vermis, and brainstem.