The diversity of hereditary neuromuscular diseases: Experiences from molecular diagnosis
Background: Hereditary neuromuscular diseases (NMDs) are a group of rare disorders, and the diagnosis of these diseases is a substantial burden for referral centers. Although next-generation sequencing (NGS) has identified a large number of genes associated with hereditary NMDs, the diagnostic rates...
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Elsevier
2022-12-01
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| Series: | Journal of the Formosan Medical Association |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0929664622002522 |
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| author | Hsueh-Wen Hsueh Wen-Chin Weng Pi-Chuan Fan Yin-Hsiu Chien Feng-Jung Yang Wang-Tso Lee Ru-Jen Lin Wuh-Liang Hwu Chih-Chao Yang Ni-Chung Lee |
| author_facet | Hsueh-Wen Hsueh Wen-Chin Weng Pi-Chuan Fan Yin-Hsiu Chien Feng-Jung Yang Wang-Tso Lee Ru-Jen Lin Wuh-Liang Hwu Chih-Chao Yang Ni-Chung Lee |
| author_sort | Hsueh-Wen Hsueh |
| collection | DOAJ |
| description | Background: Hereditary neuromuscular diseases (NMDs) are a group of rare disorders, and the diagnosis of these diseases is a substantial burden for referral centers. Although next-generation sequencing (NGS) has identified a large number of genes associated with hereditary NMDs, the diagnostic rates still vary across centers. Methods: Patients with a suspected hereditary NMD were referred to neuromuscular specialists at the National Taiwan University Hospital. Molecular diagnoses were performed by employing a capture panel containing 194 genes associated with NMDs. Results: Among the 50 patients referred, 43 had a suspicion of myopathy, and seven had polyneuropathy. The overall diagnostic rate was 58%. Pathogenic variants in 19 genes were observed; the most frequent pathogenic variant found in this cohort (DYSF) was observed in only four patients, and 10 pathogenic variants were observed in one patient each. One case of motor neuron disease was clinically mistaken for myopathy. A positive family history increased the diagnostic rate (positive: 72.7% vs. negative: 56.3%). Fourteen patients with elevated plasma creatine kinase levels remained without a diagnosis. Conclusion: The application of NGS in this single-center study proves the great diversity of hereditary NMDs. A capture panel is essential, but high-quality clinical and laboratory evaluations of patients are also indispensable. |
| first_indexed | 2024-04-13T12:48:50Z |
| format | Article |
| id | doaj.art-e9415976f5544e7aa9aa9ee648c8c74b |
| institution | Directory Open Access Journal |
| issn | 0929-6646 |
| language | English |
| last_indexed | 2024-04-13T12:48:50Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of the Formosan Medical Association |
| spelling | doaj.art-e9415976f5544e7aa9aa9ee648c8c74b2022-12-22T02:46:17ZengElsevierJournal of the Formosan Medical Association0929-66462022-12-011211225742583The diversity of hereditary neuromuscular diseases: Experiences from molecular diagnosisHsueh-Wen Hsueh0Wen-Chin Weng1Pi-Chuan Fan2Yin-Hsiu Chien3Feng-Jung Yang4Wang-Tso Lee5Ru-Jen Lin6Wuh-Liang Hwu7Chih-Chao Yang8Ni-Chung Lee9Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University College of Medicine, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University College of Medicine, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, TaiwanDepartment of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, TaiwanDepartment of Pediatrics, National Taiwan University College of Medicine, Taipei, TaiwanDepartment of Neurology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, TaiwanDepartment of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, TaiwanDepartment of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Corresponding author.Department of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Corresponding author. Department of Medical Genetics, National Taiwan University Hospital, 8 Chung-Shan South Road, Taipei, 10041, Taiwan.Background: Hereditary neuromuscular diseases (NMDs) are a group of rare disorders, and the diagnosis of these diseases is a substantial burden for referral centers. Although next-generation sequencing (NGS) has identified a large number of genes associated with hereditary NMDs, the diagnostic rates still vary across centers. Methods: Patients with a suspected hereditary NMD were referred to neuromuscular specialists at the National Taiwan University Hospital. Molecular diagnoses were performed by employing a capture panel containing 194 genes associated with NMDs. Results: Among the 50 patients referred, 43 had a suspicion of myopathy, and seven had polyneuropathy. The overall diagnostic rate was 58%. Pathogenic variants in 19 genes were observed; the most frequent pathogenic variant found in this cohort (DYSF) was observed in only four patients, and 10 pathogenic variants were observed in one patient each. One case of motor neuron disease was clinically mistaken for myopathy. A positive family history increased the diagnostic rate (positive: 72.7% vs. negative: 56.3%). Fourteen patients with elevated plasma creatine kinase levels remained without a diagnosis. Conclusion: The application of NGS in this single-center study proves the great diversity of hereditary NMDs. A capture panel is essential, but high-quality clinical and laboratory evaluations of patients are also indispensable.http://www.sciencedirect.com/science/article/pii/S0929664622002522Neuromuscular diseasesNext-generation sequencingMyopathyNeuropathy |
| spellingShingle | Hsueh-Wen Hsueh Wen-Chin Weng Pi-Chuan Fan Yin-Hsiu Chien Feng-Jung Yang Wang-Tso Lee Ru-Jen Lin Wuh-Liang Hwu Chih-Chao Yang Ni-Chung Lee The diversity of hereditary neuromuscular diseases: Experiences from molecular diagnosis Journal of the Formosan Medical Association Neuromuscular diseases Next-generation sequencing Myopathy Neuropathy |
| title | The diversity of hereditary neuromuscular diseases: Experiences from molecular diagnosis |
| title_full | The diversity of hereditary neuromuscular diseases: Experiences from molecular diagnosis |
| title_fullStr | The diversity of hereditary neuromuscular diseases: Experiences from molecular diagnosis |
| title_full_unstemmed | The diversity of hereditary neuromuscular diseases: Experiences from molecular diagnosis |
| title_short | The diversity of hereditary neuromuscular diseases: Experiences from molecular diagnosis |
| title_sort | diversity of hereditary neuromuscular diseases experiences from molecular diagnosis |
| topic | Neuromuscular diseases Next-generation sequencing Myopathy Neuropathy |
| url | http://www.sciencedirect.com/science/article/pii/S0929664622002522 |
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