Newly recognized exons induced by a splicing abnormality from an intronic mutation of the dystrophin gene resulting in Duchenne muscular dystrophy

A boy with the clinical phenotype of Duchenne muscular dystrophy had no detectable deletion or duplication in the dystrophin gene by the routine multiplex PCR method. In mRNA extracted from his muscle biopsy, newly recognized extra-exons of 172 bp and 202 bp were present between exon 25 and 26 suggesting a splicing abnormality. Genomic DNA of the intron 25 including the above insertions were amplified and sequenced. There was one nucleotide substitution of A-to-G at 2 Kb downstream from the 5' end of intron 25 which formed consensus dinucleotide 'GT' motif for 5' splice site resulting in aberrant splicing. This is the first patient who had a mutation at the central part of an intron of the dystrophin gene instead of at the exon-intron border.