SIZE OF THE UNSTABLE CTG REPEAT SEQUENCE IN RELATION TO PHENOTYPE ANDPARENTAL TRANSMISSION IN MYOTONIC-DYSTROPHY

A clinical and molecular analysis of 439 individuals affected with myo tonic dystrophy, from 101 kindreds, has shown that the size of the uns table CTG repeat detected in nearly all cases of myotonic dystrophy is related both to age at onset of the disorder and to the severity of t he phenotype. The largest repeat sizes (1.5-6.0 kb) are seen in patien ts with congenital myotonic dystrophy, while the minimally affected pa tients have repeat sizes of <0.5 kb. Comparison of parent-child pairs has shown that most offspring have an earlier age at onset and a large r repeat size than their parents, with only 4 of 182 showing a definit e decrease in repeat size, accompanied by a later age at onset or less severe phenotype. Increase in repeat size from parent to child is sim ilar for both paternal and maternal transmissions when the increase is expressed as a proportion of the parental repeat size. Analysis of co ngenitally affected cases shows not only that they have, on average, t he largest repeat sizes but also that their mothers have larger mean r epeat sizes, supporting previous suggestions that a maternal effect is involved in the pathogenesis of this form of the disorder.