A mutation in the filamin c gene causes myofibrillar myopathy with lower motor neuron syndrome: a case report

Fig. 1. Clinical pattern of the patient. Distal limb weakness affecting both upper and lower extremities, with conspicuous muscle atrophy were seen (a: gastrocnemius and anterior tibial muscles, b: interosseus muscles of the hand)

Fig. 2. Transverse T2-weighted and TIRM sequence muscle magnetic resonance images. A slightly increased signal was detected in the posterior compartment of the thigh, in the semimembranosus and semitendinosus muscles (a: T2-weighted, b: TIRM). A highly increased signal intensity in TIRM sequences was detected at the level of the lower leg, indicating obvious muscular edema (d). A mild increase in the signal intensity was observed in the T2 sequence of soleus and tibialis anterior muscles, indicating fat replacement (c)

Fig. 3. Histopathological examination of the skeletal muscles. a: HE staining showing muscle fibers of variable sizes, abnormal material deposits (white arrow), and angular atrophic fibers (red arrow). b: MGT staining showing purple myofibrillary inclusions. c: NADH-TR staining showing reduced oxidative enzyme activities in some fibers, visible as core-like lesions (red arrow). d: Immunohistochemistry staining with an anti-FLNC antibody revealing immunoreactive deposits at both subsarcolemmal and sarcoplasmic levels. e: Ultrastructural analysis of a muscle fiber showing myofibrillar disorganization (arrows) and submuscular lipofuscin deposition (star). Magnification, × 5000

Fig. 4. Molecular consequences of the FLNC c.7123G > A, p.V2375I mutation. The mutation is located in the 21st Ig-like repeated domain (a). DNA sequencing analysis showed a heterozygous missense mutation (c.7123G > A) in FLNC (red arrows) (b). Partial amino acid sequence alignment of the 21st Ig-like repeat domain of filamin proteins from various species (c)