Analysis of ERDA1, CTG18.1, and uncloned CAG/CTG repeat sequences in familial Parkinson's disease with anticipation

In several neurodegenerative diseases, anticipation or increase in disease severity in succeeding generations within families correlates with expansio ns of an intragenic CAG/CTG: repeal sequence above the normal. range throug h the generations of a pedigree, Some kindreds of familial Parkinson's dise ase (PD) exhibit genetic anticipation. We used the repeat expansion detecti on (RED) method to detect repeat expansions directly in DNA samples from th e index cases of 34 different PD families with anticipation. The mean age a t onset of the younger probands was 48.8 +/- 10.8 years and the mean interg enerational difference was 19.2 +/- 10 years. The distribution of the RED p roducts greater than 40 repeats was not significantly different between pat ients and controls with the Mann-Whitney U test (U = 510.5, p = 0.67). The samples were then screened for the two expanded-repeat loci, ERDA1 and CTG1 8.1. We found that in all cases the repeat expansion detected by the RED me thod may be accounted for by an expansion at these loci. Our results demons trate that unstable CAG/CTG expansions corresponding to uncloned or cloned sequences (ERDA1, CTG18.1) are not involved in the etiology of rare familia l case of PD with genetic anticipation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:738-741, 1999 (C) 1999 Wiley-Liss, Inc.