Interrupted CTG repeats in the 37-43 units size range in the 3'UTR of DMPK are common alleles.

The size of non-pathogenic CTG repeats in the 3'UTR of the DMPK gene varies from 5-35, whereas repeats over 50 units are pathogenic. The Intermediate repeats of 36-50 are considered 'premutation', as they are present in individuals unaffected by myotonic dystrophy, but are prone to further enlargement into the pathogenic range upon transmission to offspring. In this study, we showed that CCGCTG interrupted intermediate repeats, in the repeat size of 37-43 units, have been detected in multiple families with a history of myotonic dystrophy. However, segregation and microsatellite marker analysis of these interrupted intermediate alleles revealed that these alleles are not the same alleles (haplotypes) that were found expanded in affected family members. In contrast to the pure intermediate alleles, the CCGCTG intermediate repeats within families did not show intergenerational variability in size. Furthermore, we showed that the CCGCTG interrupted intermediate alleles have an allele frequency of approximately 0.35% in the general population, while CCGCTG interruptions were not detected in pathogenic repeat expansions over 50 repeat units in our control cohort. We postulate that intermediate repeats of size 37-43 having CCGCTG interruptions are not prone to further expansion, and therefore not act as premutations, which has great relevance for individuals with these alleles and has implications for genetic counseling and testing.