FSHD ASSOCIATED DNA REARRANGEMENTS ARE DUE TO DELETIONS OF INTEGRAL COPIES OF A 3.2 KB TANDEMLY REPEATED UNIT

Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disor der characterized by progressive weakness of the facial, shoulder and upper arm muscles. The disease is associated with DNA rearrangements w hich are detectable using probe p13E-11 (D4F104S1) in DNA digested wit h EcoRI or other restriction enzymes. We have cloned and characterized the rearranged EcoRI fragment of four unrelated FSHD patients. Restri ction fragment mapping and DNA sequence analysis showed that the proxi mal and distal parts of the EcoRI fragment, which flank a region of ta ndemly repeated 3.2 kb units, are identical in normal and rearranged E coRI fragments. These results strongly support the hypothesis that the FSHD associated rearrangements are due to deletions of integral copie s of the 3.2 kb repeated unit. Since these repeated units are likely t o form part of the FSHD transcription unit, the variation in repeat un it number might affect the function of the gene product. Hence, our da ta confine the FSHD gene region and thus provide a starting point for cloning the FSHD gene.