Searching for modulating effects of SCA2, SCA6 and DRPLA CAG tracts on the Machado-Joseph disease (SCA3) phenotype.
BACKGROUND
Machado-Joseph disease (MJD/SCA3) is an autosomal dominant cerebellar ataxia of adult onset. The variability in age at onset and the complex and heterogeneous neurologic findings indicate that MJD, caused by a major gene, is modulated by modifier factors.


OBJECTIVE
To study if the polymorphic CAG repeats at other loci (namely, SCA2, SCA6 and DRPLA) thus acted as modifier factors of this disease.


METHODS
Case-control.


METHODS
Ambulatory care in a referral center.


METHODS
A convenience sample of 39 unrelated, Brazilian patients with MJD.


METHODS
age of onset, anticipation, clinical subtypes and neurological findings.


RESULTS
Fasciculations were associated with CAG repeat length of the long SCA2 allele (Mann-Whitney U-test, P < 0.03, after Bonferroni procedure). Other measures (age of onset, anticipation, clinical types and other neurological signs) were not associated with CAG repeat length of SCA2, SCA6 and DRPLA genes.


CONCLUSIONS
The present results show that the CAG tract of SCA2 gene interferes with MJD phenotype. Further studies, with patients of other origins and with typing of other (CAG)n loci, are necessary.
Jardim
L
L
Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Brazil. laurajardim@terra.com.br
Silveira
I
I
Pereira
M L
ML
do Céu Moreira
M
M
Mendonça
P
P
Sequeiros
J
J
Giugliani
R
R
D017668:Age of Onset; D000067528:Ataxins; D015220:Calcium Channels / Q000235:genetics*; D016022:Case-Control Studies; D006801:Humans; D017827:Machado-Joseph Disease / Q000209:etiology / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011379:Prognosis; D011506:Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D018911:Trinucleotide Repeats / Q000235:genetics*; D020864:Calcium Channels, N-Type
D000067528:Ataxins; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D011506:Proteins; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C095278:atrophin-1