Figure 1.

(A) Patient with FHL1 mutation: index case. Muscle CT imaging of the neck (a), left thigh (b), pelvis (c), lower legs (d), and abdominal (e) muscles. In the neck, there is a relative preservation of the left sternocleidomastoideus (1) and almost complete involvement of all the other muscles (a). In the left thigh, only the rectus femoris (2) and vastus lateralis (3) are relatively spared (b). In the pelvis (c) and in the abdomen (e), there is a marked degeneration of all muscles. In the lower legs, only the peroneus (4) of the right leg is relatively spared (d). (B) Histochemistry and immunohistochemical analysis of patient muscle biopsy. Cross-sections show the presence of RBs in several muscle fibers, as revealed by menadione-NBT staining (a). Granular deposits are detectable at the nuclear rim of some myonuclei (a, inset). RBs appear devoid of oxidative activity (cytochrome oxidase, COX in b) and display affinity to Congo red staining (c). Immunofluorescence analysis of FHL1 shows protein accumulation throughout the cytoplasm of several muscle fibers (d) and around myonuclei (d, inset). FHL1 immunolabeling (e), followed by menadione-NBT staining (f), demonstrates that FHL1 accumulates in RBs (f). Double labeling for FHL1 and desmin (g–i) shows a marked increase of desmin in FHL1-accumulating myofibers. Scale bar, 20 μm.