Fig. 5

Histological and genetic basis of TPM3-related myopathy. A The assessment of distinct structural abnormalities in muscle histology has been historically used as a diagnostic tool for congenital myopathies. Congenital fiber type disproportion (CFTD) is the most common diagnosis in TPM3-related myopathy (51%), followed by nemaline myopathy (29%) and cap myopathy (13%). Both cap-like structures and nemaline rods can be simultaneously present in muscle biopsies (2%). In some biopsies, the diagnosis was classified as undefined (5%). Regardless of the diagnosis, variation in fiber size (also known as fiber size disproportion) with hypotrophy of type 1 muscle fibers was observed in most biopsies. These panels were generated based on n = 86 muscle biopsies from the literature. B A total of thirty-six TPM3 mutations either classified as pathogenic or likely pathogenic have been associated with the features of congenital myopathy in the literature. This represents 99 patients (n = 99) and 65 families (n = 65) documented (references [23, 28, 29, 43, 46, 88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126] as of August 2023). The p.Arg168 residue in exon 5 has been described as a mutational hotspot, documented in 41% of patients and in 30 families (colored in red). C The diagnosis (based on muscle biopsy) for each mutation is presented (colored in blue). There exists no clear genotype–histological correlation