Single sperm analysis of the CAG repeats in the gene for dentatorubral-pallidoluysian atrophy (DRPLA): the instability of the CAG repeats in the DRPLA gene is prominent among the CAG repeat diseases

Dentatorubral-pallidoluysian atrophy (DRPLA) is known to show the most prom inent genetic anticipation among CAQ repeat diseases, To investigate the me chanism underlying the meiotic instability of expanded CAG repeats ire the gene for DRPLA, we determined the CAG repeat sizes of 427 single sperm from two individuals with DRPLA. The mean variance of the change in the CAG rep eat size in sperm from the DRPLA patients (288.0) was larger than any varia nces of the CAG repeat size in sperm from patients with Machado-Joseph dise ase (38,5), Huntington's disease (69.0) and spinal and bulbar muscular atro phy (16.3), which is consistent with the clinical observation that the gene tic anticipation on the paternal transmission of DRPLA is the most prominen t among CAG repeat diseases, The variance of the change in CAG repeat size was significantly different between the two DRPLA patients (F-test, P < 0.0 001). However, the segregation ratio of single sperm with an expanded allel e to ones with a normal allele is not statistically different (P = 0.161) f rom the expected 1:1 segregation ratio, and thus segregation distortion of expanded alleles in meiosis in male patients with DRPLA was not demonstrate d.