Uninterrupted CCTG tracts in the myotonic dystrophy type 2 associated locus

Myotonic dystrophy comprises at least two genetically distinct forms, DM1 and DM2. DM2 is caused by expansion of the (CCTG)n repeat tract in the CNBP gene. The CCTG tract is generally interrupted in healthy range alleles by GCTG, TCTG or ACTG motifs. However, alleles with uninterrupted tracts have been reported on expanded alleles, and occasionally on large-sized healthy range alleles. Therefore, these uninterrupted large-sized alleles have been considered to be possible DM2 premutations. In comparison to previous studies, we identified a wider range and a higher frequency of healthy range alleles containing uninterrupted CCTG tracts. They are most likely not restricted only to large alleles, as they constantly exist in the whole spectrum of healthy range alleles. Our results indicate that the boundary between stable and unstable uninterrupted healthy range alleles is approximately 30 CCTG repeats. This suggests a similar distribution of healthy range, premutation and mutation range uninterrupted DM2 alleles, which is also typical for DM1 alleles. Interrupted alleles, and those uninterrupted with less than approximately 30 CCTG repeats, appear stable, while instability increases with increasing length of uninterrupted parts above this threshold. Unstable DM2 premutation alleles can range from approximately 30 to 55 CCTG repeats.