Evidence for a Dystrophin Missense Mutation as a Cause of X-Linked Dilated Cardiomyopathy

Background X-linked dilated cardiomyopathy (XLCM) has previously been shown to be due to mutations in the dystrophin gene, which is located at Xp21. Mutations in the 5′ portion of the gene, including the muscle promoter, exon 1, and the exon 1–intron 1 splice site, have been reported previously. The purpose of this study was to analyze the originally described family with XLCM (and others) for dystrophin mutations. Methods and Results Polymerase chain reaction (PCR) was used to amplify genomic DNA, and reverse-transcriptase PCR amplified cDNA from RNA obtained from heart and lymphoblastoid cell lines. Primers to the muscle promoter, brain promoter, and Purkinje cell promoter were designed, in addition to the exon 1 to exon 14 regions of dystrophin. Single-strand conformation polymorphism analysis was used for mutation detection, and DNA sequencing defined the mutation. Protein modeling was used for amino acid and secondary structure analysis. A missense mutation in exon 9 at nucleotide 1043 was identified...