PMC5534468_01
General appearance (A-F) and chest CT scans at the Th10-11 level (G,H) of Patient 1. (A-C) Evident amyotrophia in paravertebral muscles primarily of the thoracic spine. (D) Moderate amyotrophias in muscles of the shoulder girdle and proximal regions of the upper extremities. (E,F) Moderate pseudohypertrophy of deltoid and triceps muscles of the arm, quadriceps muscles of the thigh, and the gastrocnemius muscles. (G,H) A reticulo-nodular pattern in the form of slightly outlined centrilobular foci and subsegmental atelectasis in the basal areas of both lungs.
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F2
Patient 1 (Figures 2A-C) exhibited a delay in independent walking until 2.5 years old (y.o.). Shoulder girdle and upper extremity proximal muscles exhibited moderate amyotrophy (Figure 2D), amyotrophy was also evident in the primarily thoracic spine's paravertebral muscles. Moderate pseudohypertrophy of deltoid, triceps, quadriceps, and the gastrocnemius muscles was observed (Figures 2E,F).
Sequence of the PLEC, isoform 1f from Patient 1 cDNA. The novel apparently homozygous mutation NM_201378.3:c.58G>T, NP_958780.1:p.Glu20Ter in PLEC isoform 1f was found and classified as a likely pathogenic variant according to the criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
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F3
Disorganization of Patient 1 muscle fiber cytoskeleton due to the loss of plectin. (A-1) Immunostaining with antibodies against plectin showed plectin loss in muscle fiber sarcolemma and plectin aggregation within the sarcoplasm. (A-2) Control immunostaining with antibodies against plectin. (B-1) Immunostaining with antibodies against desmin indicated loss (asterisk) and accumulation of desmin along the periphery (arrowhead). (B-2) Control immunostaining with antibodies against desmin. (C-1) Immunostaining with antibodies against PCNA showed the tendency toward decreased proliferative activity of cells of a muscular differon and in the endomysium, enhanced proliferation of the endothelium. (C-2) Control immunostaining with antibodies against PCNA. Transmission electron microscopy showed dystrophic and destructive changes, Z-line disorganization [(D), asterisk] and small, electron-dense mitochondria located in clusters under the sarcolemma and between sarcomeres [(E), asterisk].
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F4
Z-line disorganization was identified, as well as thinned myofibrils with enlarged spaces between them (Figure 4D). Up to 30 mitochondria were observed and found to be small, electron-dense, and located in clusters under the sarcolemma and between sarcomeres (Figure 4E).