Identification and characterisation of human dysferlin transcript variants: implications for dysferlin mutational screening and isoforms.

In conducting dysferlin mutational screening using blood mRNA instead of genomic DNA, we identified the occurrence of alternative splicing involving novel dysferlin exons, i.e. exons 5a and 40a, in addition to previously reported alternative splicing of exon 17. Further study employing long range RT-PCR and subcloning revealed a total of fourteen dysferlin transcripts with maintained dysferlin reading frame. The study also characterised the differences in relative frequencies of the dysferlin transcripts in skeletal muscle and blood. The findings have potential implications for molecular diagnosis of dysferlinopathy and the identification of dysferlin isoforms.