PMC9087226_01
Muscle biopsy evaluation. (A) Frozen sections stained with H&E show the typical
features of muscular dystrophy: fiber size variation due to atrophic and hypertrophic
fibers, myonecrosis, regeneration, endomysial fibrosis and increased internal nuclei.
(B, C). Immunofluorescence staining with the anti-alpha-dystroglycan antibody IIH6 shows
bright circumferential staining of the sarcolemmal surface in control muscle (B) and a
mosaic pattern of variably reduced staining in the patient's muscle (C). The size bars
in panels A and C are 50 microm long. (D) Western blotting of wheat germ agglutinin (WGA)
preparations of frozen muscle homogenates show reduced molecular weight
alpha-dystroglycan (alphaDG) in the LGMDR9 samples (homozygous L276I and compound
heterozygous L276I/E389*) when blotted with the AF6868 antibody that binds to amino acid
epitopes in both alphaDG and betaDG. Both LGMDR9 samples have reduced to absent binding to the
glycosylation-dependent IIH6 antibody. C = normal control muscle;
alphaDG = alpha-dystroglycan; betaDG = beta-dystroglycan.
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fig1-2329048X221097518
He underwent vastus lateralis muscle biopsy with histopathology consistent with a dystrophic process (fiber size variation due to atrophic and hypertrophic fibers, endomysial fibrosis and increased internal nuclei; see Figure 1A) and immunostaining suggestive of a dystroglycanopathy [reduced staining for alpha-dystroglycan using a glycoepitope specific antibody (Figure 1C) with normal dystrophin, emerin, merosin, beta-dystroglycan and sarcoglycans staining]. Western blotting confirmed the hypoglycosylation of alpha-dystroglycan (Figure 1D).
PMC9087226_02