MOLECULAR ANALYSIS OF BRITISH FACIOSCAPULOHUMERAL DYSTROPHY FAMILIES FOR 4Q DNA REARRANGEMENTS

Facioscapulohumeral muscular dystrophy is an important autosomal domin ant neuromuscular disorder that has been localised to 4q35. We have an alysed our extensive panel of 45 families with a new DNA marker p13E-1 1. The findings, based on multiply informative individual meioses and multipoint mapping, suggest that probe p13E-11 is the closest marker f or the disorder and it is likely to be located proximal to the disease locus as are all the other present markers. In nine of the ten new mu tations studied, a new smaller EcoRI fragment which was not present in either of the parents was detected, indicating that a de novo DNA rea rrangment is indeed associated with the development of the disease sta te. However, in view of the difficulty in defining the size of over 30 kb alleles and the recombinant events observed with p13E-11, we sugges t that it should be used in combination with another VNTR marker until a close distal flanking marker for this condition is identified or th e gene itself is isolated.