Novel cryptic exons identified in introns 2 and 3 of the human dystrophin gene with duplication of exons 8-11

Abstract

The dystrophin gene, which is mutated in Duchenne muscular dystrophy, is the largest known human gene and characterized by the huge size of its introns. Intron 2 has been shown to include cryptic exons termed exons 2a and 2b, while intron 3 has been shown to include a cryptic exon designated exon 3a. In the present study, we identified 2 and 1 additional cryptic exons in introns 2 and 3, respectively. A previously unknown 157-bp insertion was identified between exons 2 and 3 of a dystrophin mRNA isolated from the lymphocytes of a dystrophinopathy patient with duplication of exons 8-11. Since this sequence exhibited the typical characteristics of a genomic exon, we designated it "exon 2c-l". A more detailed examination revealed that a position 4 bp downstream from the 5' end of exon 2c-l was also used as a splice acceptor site, and this exon was designated "exon 2c-s". In the same patient, a 357-bp insertion was identified between exons 3 and 4. Since this sequence also showed the typical characteristics of an exon, and its 3' end was the same as the splice donor site of exon 3a, we designated the novel cryptic exon "exon 3a-l", and changed the name of the previously reported exon 3a to "exon 3a-s". Among these novel cryptic exons, exon 3a-l was also incorporated into the dystrophin mRNA from normal lymphocytes, whereas exons 2c-l and 2c-s were not. The physiological or pathophysiological roles of these novel cryptic exons remain to be clarified.