For example, the myotonia in DM1 is often quite severe in distal limb and oromandibular muscles, which now can be attributed to combined ClC-1 loss and CaV1.1 e29 skipping in those muscles, whereas in proximal limb muscles, the myotonia and weakness are much less apparent. This evidence concerns the gene CACNA1S and myotonic dystrophy type 1.