Novel dystrophin mutations revealed by analysis of dystrophin mRNA: alternative splicing suppresses the phenotypic effect of a nonsense mutation

The complete dystrophin mRNA sequence has been analyzed in 20 Duchenne musc ular dystrophy and Becker muscular dystrophy patients. In 13 cases, deletio ns in mRNA were detected using reverse transcription-polymerase chain react ion and in another seven cases, point mutations were found using the protei n truncation test. Sixteen patients diagnosed with Duchenne muscular dystro phy showed the presence of deletions or of nonsense point mutations. From f our patients with the Becker muscular dystrophy phenotype, three cases were associated with deletions conserving the translational frame and one was a ssociated with a nonsense mutation E1110X. In the case of the E1110X mutati on, an alternative splicing of dystrophin mRNA (3485-3640del) was detected in this patient which included the E1110X mutation site (nucleotide 3536) a nd did not change the translation reading frame. Individual nonsense point mutations were characterized by sequence analysis, which showed five novel mutations with respect to those reported in the Cardiff Human Gene Mutation Database http://uwcm.web.cf.ac.uk/uwcm/mg/hgmd0.html and the Leiden muscul ar dystrophy pages http://www.dmd.nl/. (C) 2001 Elsevier Science B.V. All r ights reserved.