The evaluation of polyglutamine repeats in autosomal dominant Parkinson's disease

Abstract We evaluated the contributions of various polyglutamine (polyQ) disease genes to Parkinson's disease (PD). We compared the distributions of polyQ repeat lengths in 8 common genes ( ATXN1 , ATXN2 , ATXN3 , CACNA1A , ATXN7 , TBP , ATN1 , and HTT ) in 299 unrelated patients with autosomal dominant PD (ADPD) and 329 normal controls. We also analyzed the possibility of genetic interactions between ATXN1 and ATXN2 , ATXN2 and ATXN3 , and ATXN2 and CACNA1A . Intermediate-length polyQ expansions (>24 Qs) of ATXN2 were found in 7 ADPD patients and no controls (7/299 = 2.34% and 0/329 = 0%, respectively; p = 0.0053 < 0.05/8 after Bonferroni correction). These patients showed typical L-DOPA-responsive PD phenotypes. Conversely, no significant differences in polyQ repeat lengths were found between the ADPD patients and the controls for the other 7 genes. Our results may support the hypothesis that ATXN2 polyQ expansion is a specific predisposing factor for multiple neurodegenerative diseases.