Rare clinical phenotype of filaminopathy presenting as restrictive cardiomyopathy and myopathy in childhood

Figures

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  Fig. 1. Cardiac imaging features of restrictive cardiomyopathy in Patient 7 (b, c, e, f) and Patient 10 (a, d). Images of patient 10 corresponding to four-chamber view (a) and Pulsed Way Doppler on mitral valve (d) confirmed atrial enlargement and moderate left ventricle diastolic dysfunction. Echocardiography pictures of patient 7 (b, c) corresponding to four-chamber view (b) and short-axis view with Color Doppler (c) also confirmed atrial enlargement with normal ventricle wall thickness and severe tricuspid valve regurgitation. Cardiac MRI images of patient 7 (e, f) demonstrating atrial enlargement and normal ventricle wall thickness. RA right atrium, LA left atrium, RV right ventricle, LV left ventricle, TV tricuspid valve

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  Fig. 2. Clinical manifestations of FLNC filaminopathy. a Patient no. 3, deformity of the chest and spine (grade IV scoliosis). b Patient no. 2, signs of central tetraparesis, spasticity with myoclonus of the arms and legs, kyphoscoliosis. c, e Patient no. 12, arthrogryposis with joint deformity. d Patient no. 6, camptodactyly of the thumbs on both hands (reproduced from Vershinina et al. Pediatria 2020, 10.24110/0031-403X-2020-99-3-88-95 [63] permission applied)

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  Fig. 3. a Mutation plot and domain organization of the FLNC protein sequence performed using the UniProt database. CH calponin homology domain is marked with green; the ROD1 and ROD2 domains are marked with red, Ig-like domains are numbered from 1 to 24; the dimerization domain is marked with brown. Variants are mapped to the protein structure. b All missense variants were located in conserved regions among different species

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  Fig. 4. Views of the homology model of domain pairs of IgFLNc9–IgFLNc10, where domains 9 and 10 are shown as cartoons and colored in orange and light blue, respectively. The domain-domain interfaces are highlighted with green. Residues are shown as sticks. A1183 and A1186 are shown as ball and sticks; mutations A1186V and A1183L are colored with magenta

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  Fig. 5. Views of the homology model of IgFLNc20-IgFLNc21, where domains 20 and 21 are shown as cartoons and colored in orange and lightblue, respectively. The domain-domain interface are highlighted in green. Residues are shown as sticks. V2297, G2151, and T2287 are shown as ball and sticks; mutations V2297M, T2287P, G2151S are colored with magenta. Note that the CD face of IgFLNc21 is blocked by strand A of IgFLNc20. An insertion of 82 amino acids in IgFLNc20 is shown by dashed line. It is a specific insertion which is absent in filamin A and filamin B