Pulsed-field gel electrophoresis of the D4F104S1 locus reveals the size and the parental origin of the facioscapulohumeral muscular dystrophy (FSHD)-associated deletions.

Recently, probe p13E-11 (D4F104S1) was shown to identify de novo DNA rearrangements, which are associated with the development of facioscapulohumeral muscular dystrophy (FSHD). These rearrangements are likely to become instrumental in cloning the FSHD gene itself. Analysis by pulsed-field gel electrophoresis demonstrates that p13E-11 recognizes two highly polymorphic loci, with HindIII restriction fragments ranging in size from about 30 to 320 kb. Haplotype analysis unambiguously assigned one of the two loci to chromosome 4q35. The detection of identical NotI or NruI fragments with both CEB8 (D4F35S1) and p13E-11 demonstrated that the DNA rearrangements are deletions that are restricted to the HindIII fragments detectable by p13E-11. In two cases, the sizes of the deletion could be established and were found to be 25 and 85 kb in length, respectively. So far, we have been able to define the parental origin of the mutation in seven different patients and have found that in five cases the maternal allele was involved.