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

Abstract

Background: We report a patient with a novel c.737 C > T variant (p.Ser246Leu) of the TPM3 gene presenting with adult-onset distal myopathy. Case presentation: A 35-year-old Chinese male patient presentedwith a history of progressive finger weakness. Physical examination revealeddifferential finger extension weakness, together with predominant fingerabduction, elbow flexion, ankle dorsiflexion and toe extension weakness. MuscleMRI showed disproportionate fatty infiltration of the glutei, sartorius andextensor digitorum longus muscles without significant wasting. Muscle biopsy andultrastructural examination showed a non-specific myopathic pattern withoutnemaline or cap inclusions. Genetic sequencing revealed a novel heterozygousp.Ser246Leu variant (c.737C>T) of the TPM3 gene which is predicted tobe pathogenic. This variant is located in the area of the TPM3 genewhere the protein product interacts with actin at position Asp25 of actin.Mutations of TPM3 in these loci have been shown to alter the sensitivityof thin filaments to the influx of calcium ions. Conclusion: This report further expands the phenotypicspectrum of myopathies associated with TPM3 mutations, as mutations in TPM3had not previously been reported with adult-onset distal myopathy. We also discuss the interpretation of variantsof unknown significance in patients with TPM3 mutations and summarisethe typical muscle MRI findings of patients with TPM3 mutations.