CHARACTERISTICS OF INTERGENERATIONAL CONTRACTIONS OF THE CTG REPEAT IN MYOTONIC-DYSTROPHY

In myotonic dystrophy (DM), the size of a CTG repeat in the DM kinase gene generally increases in successive generations with clinical evide nce of anticipation. However, there have also been cases with an inter generational contraction of the repeat. We examined 1,489 DM parent-of fspring pairs, of which 95 (6.4%) showed such contractions in peripher al blood leukocytes (PBL). In 56 of the 95 pairs, clinical data allowe d an analysis of their anticipation status. It is surprising that anti cipation occurred in 27 (48%) of these 56 pairs, while none clearly sh owed a later onset of DM in the symptomatic offspring. The contraction occurred in 76 (10%) of 753 paternal transmissions and in 19 (3%) of 736 maternal transmissions. Anticipation was observed more frequently in maternal (85%) than in paternal (37%) transmissions (P < .001). The parental repeat size correlated with the size of intergenerational co ntraction (r(2) =.50, P much less than .001), and the slope of linear regression was steeper in paternal (-.62) than in maternal (-.30) tran smissions (P much less than .001). Sixteen DM parents had multiple DM offspring with the CTG repeat contractions. This frequency was higher than the frequency expected from the probability of the repeat contrac tions (6.4%) and the size of DM sib population (1.54 DM offspring per DM parent, in 968 DM parents). We conclude that (1) intergenerational contraction of the CTG repeat in leukocyte DNA frequently accompanies apparent anticipation, especially when DM is maternally transmitted, a nd (2) the paternal origin of the repeat and the presence of the repea t contraction in a sibling increase the probability of the CTG repeat contraction.