Expression and Splicing Analysis of Myotonic Dystrophy and Other Dystrophic Muscle

The prevailing patho-mechanistic paradigm for myotonic dystrophy (DM) is that the aberrant presence of embryonic isoforms is responsible for many, if not most, aspects of the pleiotropic disease phenotype. In order to identify such aberrantly expressed isoforms in skeletal muscle of DM type 1 (DM1) and type 2 (DM2) patients, we utilized the Affymetrix exon array to characterize the largest collection of DM samples analyzed to date, and included non-DM dystrophic muscle samples (NMD) as disease controls. For the exon array profiling on the Human Exon 1.0 ST array (Affymetrix Santa Clara, CA) we used a panel of 28 skeletal muscle biopsies from DM1 (n=8), DM2 (n=10), Becker muscular dystrophy, BMD, (n=3), Duchenne muscular dystrophy, DMD (n=1), Tibial muscular dystrophy, TMD, (n=2) and normal skeletal muscle (n=4). Normal control RNAs were purchased commercially. .CEL files were generated with a pre-commercial version of the Affymetrix processing software, and the headers might be non-standard. In our lab, users of the Partek software could use them, whereas users of GeneSpring had to modify the header information.