A novel variant in the tropomyosin 3 gene presenting as an adult-onset distal myopathy - a case report

Figures

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  Fig. 1. Physical examination findings and lower body MRI of patient. Differential asymmetric distal upper limb weakness of finger extensors and finger abductors (A). No significant atrophy is observed (B-D). Muscle MRI T1 sequence findings of patient at the level of the pelvic girdle (E), thighs (F) and calves (G). There is no significant loss of muscle volume or presence of muscle edema. E Mild symmetric fatty infiltration noted of the bilateral gluteus maximus (arrowhead) and gluteus medius (arrow). F Moderate fatty infiltration of the bilateral sartorius (solid arrowhead), mild infiltration of the adductor magnus (hollow arrowhead), posterior compartment of the thigh, particularly the bilateral semimembranosus (arrow) and biceps femoris (*). G Moderate fatty infiltration of the bilateral extensor digitorum longus muscles (solid arrowhead), mild fatty infiltration of bilateral tibialis anterior (hollow arrowhead), as well as mild fatty infiltration of the bilateral soleus muscles (arrow)

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  Fig. 2. Biceps brachii muscle biopsy from patient. A There is variation in fibre size consistent with a chronic myopathy. B No inclusions are seen on Gömöri-trichrome stain. C and F Some fibres showed pale central areas on NADH stain and SDH stains (arrows) but not on E COX staining, suggesting regions with reduced oxidative enzyme activities. D There is predominantly type 2 fibre atrophy with no fibre type predominance. (A: Hematoxylin and eosin (HE) stain, original magnification × 10; B: Gömöri-trichrome stain, original magnification × 20; C: NADH-TR stain, original magnification × 10; D: ATPase pH9.4, original magnification × 10; E: COX stain, original magnification × 10; F: SDH stain, original magnification × 10; A-F: scale bar 100mm; picture resolution A-F: 1280 x1024)

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  Fig. 3. Electron microscopy revealed fibre atrophy (arrow) without the presence of nemaline rods (scale bar 2µm)

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  Fig. 4. A Tropomyosins form α-helical coiled-coil dimers via a seven residue repeat motif in their amino acid sequence [a-b-c-d-e-f-g] [3]. This structure is stabilised by the hydrophobic interactions between a-a’ and d-d’ (shaded squares) together with the hydrophilic interactions between g-e’ and e-g’ (shaded circles) of the two tropomyosin chains. Actin binds to tropomyosin electrostatically at two points, at actin position Asp25 and a cluster of amino acids that includes actin at position Lys326. B The 3-dimensional structure of one of the two tropomyosin molecules (dark grey) interfacing with the actin double helix (light grey) at actin at position Asp25 (black) is shown here. C The α-tropomyosinslow amino acid sequence (annotated using the 1-letter amino acid abbreviation) is depicted here. The position of the amino acid in relation to the seven residue repeat motif of tropomyosin is indicated directly below the amino acid sequence. The structure of tropomyosin is further divided into seven quasi-repeating periods (periods 1-7) and α-bands and ß-bands. The purple circles highlight residues interacting with actin at position Asp25. Known pathogenic variants of the TPM3 gene that…