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

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 presented with a history of progressive finger weakness. Physical examination revealed differential finger extension weakness, together with predominant finger abduction, elbow flexion, ankle dorsiflexion and toe extension weakness. Muscle MRI showed disproportionate fatty infiltration of the glutei, sartorius and extensor digitorum longus muscles without significant wasting. Muscle biopsy and ultrastructural examination showed a non-specific myopathic pattern without nemaline or cap inclusions. Genetic sequencing revealed a novel heterozygous p.Ser246Leu variant (c.737C>T) of the TPM3 gene which is predicted to be pathogenic. This variant is located in the area of the TPM3 gene where the protein product interacts with actin at position Asp25 of actin. Mutations of TPM3 in these loci have been shown to alter the sensitivity of thin filaments to the influx of calcium ions. CONCLUSION: This report further expands the phenotypic spectrum of myopathies associated with TPM3 mutations, as mutations in TPM3 had not previously been reported with adult-onset distal myopathy. We also discuss the interpretation of variants of unknown significance in patients with TPM3 mutations and summarise the typical muscle MRI findings of patients with TPM3 mutations.

Unique Clinical, Radiological and Histopathological Characteristics of a Southeast Asian Cohort of Patients with Limb-Girdle Muscular Dystrophy 2G/LGMD-R7-Telethonin-Related.

AIM: We describe a cohort of five patients with limb-girdle muscular dystrophy (LGMD) 2G/LGMD-R7 in a South-east Asian cohort. BACKGROUND: LGMD2G/LGMD-R7-telethonin-related is caused by mutations in the TCAP gene that encodes for telethonin. METHODS: We identified consecutive patients with LGMD2G/LGMD-R7-telethonin-related, diagnosed at the National Neuroscience Institute (NNI) and National University Hospital (NUH) between January 2000 and June 2021. RESULTS: At onset, three patients presented with proximal lower limb weakness, one patient presented with Achilles tendon contractures, and one patient presented with delayed gross motor milestones. At last follow up, three patients had a limb girdle pattern of muscle weakness and two had a facioscapular humeral pattern of weakness. Whole body muscle MRI performed for one patient with a facioscapular-humeral pattern of weakness showed a pattern of muscle atrophy similar to facioscapular-humeral dystrophy. One patient had histological features consistent with myofibrillar myopathy; electron microscopy confirmed the disruption of myofibrillar architecture. One patients also had reduced staining to telethonin antibody on immunohistochemistry. CONCLUSION: We report the unique clinical and histological features of a Southeast Asian cohort of five patients with LGMD2G/LGMD-R7-telethonin-related muscular dystrophy and further expand its clinical and histopathological spectrum.