DIRECT-DETECTION OF 4Q35 REARRANGEMENTS IMPLICATED IN FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY (FSHD)

The p13E-11 probe has been shown to detect DNA rearrangements in spora dic and familial cases of FSHD. Its use, however, has been hampered by the fact that it detects at least two pairs of EcoRI alleles, one der ived from the 4q35 region (D4F104S1), the other from 10q26 (D10F104S2) . We have cloned p13E-11 EcoRI fragments from the 4q35 and 10q26 subte lomeric regions and shown the presence of several restriction site dif ferences within the KpnI tandem repeat units. The two loci present a d ifferent distribution of restriction sites for the enzyme BlnI which a llows differential cleavage of the KpnI units derived from 10q26, leav ing intact the 4q35 pair of alleles. This method of differential restr iction greatly facilitates the interpretation of Southern blots obtain ed from affected and unaffected subjects, with an important improvemen t in reliability for diagnosis and genetic counselling. In addition, t his method can be used to investigate the molecular mechanism of the 4 q35 rearrangement implicated in the disease and to ascertain whether t he rearrangement is because of interchromosomal exchange between 4qter and 10qter KpnI repeats.