Genetic and clinical correlations of Xp21 muscular dystrophy

Abstract

We have investigated over 100 patients with Xp21 muscular dystrophy, drawing together the results of detailed clinical, genetic and dystrophin investigations. A spectrum of disease severity was confirmed, with the most homogeneous clinical groups being at either end of the spectrum, represented by the typical Duchenne and Becker phenotypes. The groups in between showed clinical heterogeneity, and variability in the genetic and dystrophin results. While an out-of-frame deletion in association with undetectable dystrophin is most likely to predict the most severe phenotype, and increasing abundance of dystrophin is associated generally with a milder clinical course, no value of dystrophin abundance reliably predicts a particular phenotype. However, deletions of the dystrophin gene involving exons 45-47 and 45-48 especially do seem to be consistently associated with the mildest Becker phenotype. Additional factors must play a role in determining the exact clinical course.