Chest X-rays showing severe cardiomegaly in patient #1 (panel A) and patient #2 (panel B).

Skeletal muscle cryosections from patient #2 were stained with H&E and a panel of antibodies using immunofluorescence methodology. The muscle pathology is relatively mild for LGMD-2I (A), but more severe than in patient #1 (compare with Fig. 2A). Staining for the core domain of α-dystroglycan (D) and β-dystroglycan (E) is normal. In contrast, staining for glycosylated α-dystroglycan ranges from negative to normal in a mosaic pattern that is characteristic for LGMD-2I (VIA4-1 antibody, panel B; IIH6 antibody, panel C). Scale bars, 200 μm.

Skeletal muscle and cardiac cryosections from patient #1 and control patients were stained with H&E and a panel of antibodies using immunofluorescence methodology. While the muscle pathology in patient #1 is mild for LGMD 2I (A), the heart shows features of cardiomyopathy (variation in myocyte diameter, variation in nuclear size and shape, and fibrosis) that are relatively severe (B). Staining for dystrophin, β-dystroglycan, and the core domain of α-dystroglycan is normal in both the skeletal muscle and the heart of patient #1. In contrast, staining for glycosylated α-dystroglycan ranges from negative to normal in a mosaic pattern in patient #1’s skeletal muscle and is absent in her heart. Shown here are representative micrographs of staining with H&E (A–B) and dystrophin (C–F), glycosylated α-dystroglycan (VIA4-1, G–H; IIH6, I–J), core α-dystroglycan (GT20ADG, K–N) and β-dystroglycan antibodies (O–R). Control skeletal muscle, panels C, G, K and O. Patient #1’s skeletal muscle, panels A, D, H, L and P. Control heart, panels E, I, M and Q. Patient #1’s heart, panels B, F, J, N and R. Scale bars, 100 μm.

Paraffin sections from a control patient who was transplanted for treatment of severe ischemic cardiomyopathy (panels A and B), patient #1 (panels C and D), and patient #2 (panels E and F) were stained with H&E (panels A, C and F) or the α-dystroglycan glycoepitope specific antibody, IIH6, using an immunoperoxidase methodology (panels B, D and F). While nearly all cardiac myocytes stain strongly in the ischemic cardiomyopathy heart, α-dystroglycan is negative in both LGMD-2I patients. Scale bar, 100 μm.