Two novel mutations in TTN of a patient with congenital myopathy: A case report
Abstract Background Early‐onset myopathies show a wide spectrum of phenotypes and are composed of various types of inherited neuromuscular diseases, making it difficult to diagnose. TTN mutation‐related myopathy is a known cause of early‐onset myopathy. Since a next‐generation sequencing (NGS) has e...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.866 |
| _version_ | 1828127772567928832 |
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| author | Joon Young Jang Yulhyun Park Dae‐Hyun Jang Ja‐Hyun Jang Ju Seok Ryu |
| author_facet | Joon Young Jang Yulhyun Park Dae‐Hyun Jang Ja‐Hyun Jang Ju Seok Ryu |
| author_sort | Joon Young Jang |
| collection | DOAJ |
| description | Abstract Background Early‐onset myopathies show a wide spectrum of phenotypes and are composed of various types of inherited neuromuscular diseases, making it difficult to diagnose. TTN mutation‐related myopathy is a known cause of early‐onset myopathy. Since a next‐generation sequencing (NGS) has enabled sequencing of the vast amount of DNA, TTN, which is the longest coding sequence of any human gene, mutations can now be revealed. We report a 10‐year‐old female with severe congenital muscular weakness and delayed motor development since birth. Methods Next‐generation sequencing as well as electromyography and muscle biopsy were performed. Results To date, she is incapable of walking alone. Her younger sister had similar but more severe symptoms with respiratory failure. In electromyography, short‐duration, small‐amplitude motor unit action potential, and early recruitment patterns were observed in the involved proximal muscles, suggesting myopathy. Muscle histopathology showed a specific atrophy of increased fiber size variability, frequent nuclear internalization, as well as degeneration and regeneration of fibers with type I fiber predominance, consistent with the findings of a previous report about congenital titinopathy. A NGS study revealed two different possible pathogenic variants in TTN: (a) canonical splicing mutation in the intron 105 (c. 29963‐1G>C) and (b) frameshift and truncating mutation in the exon 339 (c.92812dup/p.Arg30938LysfsTer15). All variants were confirmed by conventional Sanger sequencing. Conclusion We propose that unbiased genomic sequencing can be helpful in screening patients with early‐onset myopathy. |
| first_indexed | 2024-04-11T15:55:37Z |
| format | Article |
| id | doaj.art-5432cf9d2f5f451ab899d5e30f47c97f |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-11T15:55:37Z |
| publishDate | 2019-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-5432cf9d2f5f451ab899d5e30f47c97f2022-12-22T04:15:11ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-08-0178n/an/a10.1002/mgg3.866Two novel mutations in TTN of a patient with congenital myopathy: A case reportJoon Young Jang0Yulhyun Park1Dae‐Hyun Jang2Ja‐Hyun Jang3Ju Seok Ryu4Department of Rehabilitation Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine Seongnam KoreaDepartment of Rehabilitation Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine Seongnam KoreaDepartment of Rehabilitation Medicine College of Medicine, The Catholic University of Korea Seoul KoreaGreen Cross Genome Yongin KoreaDepartment of Rehabilitation Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine Seongnam KoreaAbstract Background Early‐onset myopathies show a wide spectrum of phenotypes and are composed of various types of inherited neuromuscular diseases, making it difficult to diagnose. TTN mutation‐related myopathy is a known cause of early‐onset myopathy. Since a next‐generation sequencing (NGS) has enabled sequencing of the vast amount of DNA, TTN, which is the longest coding sequence of any human gene, mutations can now be revealed. We report a 10‐year‐old female with severe congenital muscular weakness and delayed motor development since birth. Methods Next‐generation sequencing as well as electromyography and muscle biopsy were performed. Results To date, she is incapable of walking alone. Her younger sister had similar but more severe symptoms with respiratory failure. In electromyography, short‐duration, small‐amplitude motor unit action potential, and early recruitment patterns were observed in the involved proximal muscles, suggesting myopathy. Muscle histopathology showed a specific atrophy of increased fiber size variability, frequent nuclear internalization, as well as degeneration and regeneration of fibers with type I fiber predominance, consistent with the findings of a previous report about congenital titinopathy. A NGS study revealed two different possible pathogenic variants in TTN: (a) canonical splicing mutation in the intron 105 (c. 29963‐1G>C) and (b) frameshift and truncating mutation in the exon 339 (c.92812dup/p.Arg30938LysfsTer15). All variants were confirmed by conventional Sanger sequencing. Conclusion We propose that unbiased genomic sequencing can be helpful in screening patients with early‐onset myopathy.https://doi.org/10.1002/mgg3.866congenital myopathieshumannext‐generation sequencingTTN |
| spellingShingle | Joon Young Jang Yulhyun Park Dae‐Hyun Jang Ja‐Hyun Jang Ju Seok Ryu Two novel mutations in TTN of a patient with congenital myopathy: A case report Molecular Genetics & Genomic Medicine congenital myopathies human next‐generation sequencing TTN |
| title | Two novel mutations in TTN of a patient with congenital myopathy: A case report |
| title_full | Two novel mutations in TTN of a patient with congenital myopathy: A case report |
| title_fullStr | Two novel mutations in TTN of a patient with congenital myopathy: A case report |
| title_full_unstemmed | Two novel mutations in TTN of a patient with congenital myopathy: A case report |
| title_short | Two novel mutations in TTN of a patient with congenital myopathy: A case report |
| title_sort | two novel mutations in ttn of a patient with congenital myopathy a case report |
| topic | congenital myopathies human next‐generation sequencing TTN |
| url | https://doi.org/10.1002/mgg3.866 |
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