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 presented with a history of progressive finger weakness. Physical examination revealed differen...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Neurology |
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| Online Access: | https://doi.org/10.1186/s12883-023-03225-3 |
| _version_ | 1797832029074620416 |
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| author | Zhiyong Chen Monica Saini Jasmine Shimin Koh Gareth Zigui Lim Nancy Jiaojiao Dang Kalpana Prasad Swee Hoon Koh Karine Su Shan Tay Ming Lee Helen Lisa Ong Yi Zhao Ankit Tandon Josiah Yui Huei Chai |
| author_facet | Zhiyong Chen Monica Saini Jasmine Shimin Koh Gareth Zigui Lim Nancy Jiaojiao Dang Kalpana Prasad Swee Hoon Koh Karine Su Shan Tay Ming Lee Helen Lisa Ong Yi Zhao Ankit Tandon Josiah Yui Huei Chai |
| author_sort | Zhiyong Chen |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-04-09T14:01:09Z |
| format | Article |
| id | doaj.art-7ca7f92fbd3944b0bcbf8f0ad5df08b7 |
| institution | Directory Open Access Journal |
| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-04-09T14:01:09Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj.art-7ca7f92fbd3944b0bcbf8f0ad5df08b72023-05-07T11:16:33ZengBMCBMC Neurology1471-23772023-05-012311810.1186/s12883-023-03225-3 A novel variant in the tropomyosin 3 gene presenting as an adult-onset distal myopathy - a case reportZhiyong Chen0Monica Saini1Jasmine Shimin Koh2Gareth Zigui Lim3Nancy Jiaojiao Dang4Kalpana Prasad5Swee Hoon Koh6Karine Su Shan Tay7Ming Lee8Helen Lisa Ong9Yi Zhao10Ankit Tandon11Josiah Yui Huei Chai12Department of Neurology, National Neuroscience InstituteDepartment of Neurology, National Neuroscience InstituteDepartment of Neurology, National Neuroscience InstituteDepartment of Neurology, National Neuroscience InstituteDepartment of Neurology, National Neuroscience InstituteDepartment of Neurology, National Neuroscience InstituteNeuromuscular Laboratory, National Neuroscience InstituteNeuromuscular Laboratory, National Neuroscience InstituteDepartment of Pathology, Singapore General HospitalDepartment of Clinical and Translational Research, Singapore General HospitalDepartment of Clinical and Translational Research, Singapore General HospitalDepartment of Diagnostic Radiology, Tan Tock Seng HospitalDepartment of Neurology, National Neuroscience InstituteAbstract 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.https://doi.org/10.1186/s12883-023-03225-3Congenital myopathyDistal myopathyTropomyosinTPM3Case report |
| spellingShingle | Zhiyong Chen Monica Saini Jasmine Shimin Koh Gareth Zigui Lim Nancy Jiaojiao Dang Kalpana Prasad Swee Hoon Koh Karine Su Shan Tay Ming Lee Helen Lisa Ong Yi Zhao Ankit Tandon Josiah Yui Huei Chai A novel variant in the tropomyosin 3 gene presenting as an adult-onset distal myopathy - a case report BMC Neurology Congenital myopathy Distal myopathy Tropomyosin TPM3 Case report |
| title | A novel variant in the tropomyosin 3 gene presenting as an adult-onset distal myopathy - a case report |
| title_full | A novel variant in the tropomyosin 3 gene presenting as an adult-onset distal myopathy - a case report |
| title_fullStr | A novel variant in the tropomyosin 3 gene presenting as an adult-onset distal myopathy - a case report |
| title_full_unstemmed | A novel variant in the tropomyosin 3 gene presenting as an adult-onset distal myopathy - a case report |
| title_short | A novel variant in the tropomyosin 3 gene presenting as an adult-onset distal myopathy - a case report |
| title_sort | a novel variant in the tropomyosin 3 gene presenting as an adult onset distal myopathy a case report |
| topic | Congenital myopathy Distal myopathy Tropomyosin TPM3 Case report |
| url | https://doi.org/10.1186/s12883-023-03225-3 |
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