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

Abstract

In several neurodegenerative diseases, anticipation or increase in disease severity in succeeding generations within families correlates with expansions of an intragenic CAG/CTG repeat sequence above the normal range through the generations of a pedigree. Some kindreds of familial Parkinson's disease (PD) exhibit genetic anticipation. We used the repeat expansion detection (RED) method to detect repeat expansions directly in DNA samples from the index cases of 34 different PD families with anticipation. The mean age at onset of the younger probands was 48.8 +/- 10.8 years and the mean intergenerational difference was 19.2 +/- 10 years. The distribution of the RED products greater than 40 repeats was not significantly different between patients 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 CTG18.1. We found that in all cases the repeat expansion detected by the RED method may be accounted for by an expansion at these loci. Our results demonstrate that unstable CAG/CTG expansions corresponding to uncloned or cloned sequences (ERDA1, CTG18.1) are not involved in the etiology of rare familial case of PD with genetic anticipation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:738-741, 1999