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Replication errors may contribute to the generation of large deletions and duplications in the dystrophin gene

Frequent recurrent mutations of the human dystrophin gene lead to Duchenne and Becker muscular dystrophies. Although the ˜ 2.5 Mb size of the gene may form a large targe for mutations it is not clear to date which mechanisms promote the observed high frequency of spontaneous mutants (1 in 10,000 X‐chromosomes) of which a high percentage ( > 70%) are gross structural aberrations (deletions/duplications). In order to gain insight into possible molecular mechanisms we have cloned and sequenced the deletion junction fragments from two unrelated Duchenne patients. Our data, together with a short review on other cases from the literature, present evidence that errors of DNA replication may contribute to the generation of submicroscopic chromosome rearrangements. © 1992 Wiley‐Liss, Inc.