Mapping of four translocation breakpoints within the Duchenne muscular dystrophy gene

Abstract

There are over 20 females with Duchenne or Becker muscular dystrophy (DMD or BMD) who have X-autosome translocations that break the X chromosome within band Xp21. Several of these translocations have been mapped with genomic probes to regions throughout the large (approximately 2000 kb) DMD gene. In this report, a cDNA clone from the 5' end of the gene was used to further map the breakpoints in four X-autosome translocations. A t(X;21) translocation in a patient with BMD and a t(X;1) translocation in a patient with DMD were found to break within a large 110-kb intron between exons 7 and 8. Two other DMD translocations, t(X;5) and t(X;11), were found to break between the first and the second exon of the gene within a presumably large intron (greater than 100 kb). These results demonstrate that all four translocations have disrupted the DMD gene and make it possible to clone and sequence the breakpoints. This will in turn determine whether these translocations occur by chance in these large introns or whether there are sequences that predispose to translocations.