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Phenotypic heterogeneity in patients with NEFL‐related Charcot–Marie–Tooth disease
Charcot–Marie–Tooth disease (CMT) is the most common hereditary peripheral neuropathy. Mutations in the neurofilament light polypeptide (NEFL) gene produce diverse clinical phenotypes, including demyelinating (CMT1F), axonal (CMT2E), and intermediate (CMTDIG) neuropathies. From 2005 to 2020, 1,143 K...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830812/ https://www.ncbi.nlm.nih.gov/pubmed/35044100 http://dx.doi.org/10.1002/mgg3.1870 |
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author | Kim, Hye Jin Kim, Sang Beom Kim, Hyun Su Kwon, Hye Mi Park, Jae Hong Lee, Ah Jin Lim, Si On Nam, Soo Hyun Hong, Young Bin Chung, Ki Wha Choi, Byung‐Ok |
author_facet | Kim, Hye Jin Kim, Sang Beom Kim, Hyun Su Kwon, Hye Mi Park, Jae Hong Lee, Ah Jin Lim, Si On Nam, Soo Hyun Hong, Young Bin Chung, Ki Wha Choi, Byung‐Ok |
author_sort | Kim, Hye Jin |
collection | PubMed |
description | Charcot–Marie–Tooth disease (CMT) is the most common hereditary peripheral neuropathy. Mutations in the neurofilament light polypeptide (NEFL) gene produce diverse clinical phenotypes, including demyelinating (CMT1F), axonal (CMT2E), and intermediate (CMTDIG) neuropathies. From 2005 to 2020, 1,143 Korean CMT families underwent gene sequencing, and we investigated the clinical, genetic, and neuroimaging spectra of NEFL‐related CMT patients. Ten NEFL mutations in 17 families (1.49%) were identified, of which three (p.L312P, p.Y443N, and p.K467N) were novel. Eight de novo cases were identified at a rate of 0.47 based on a cosegregation analysis. The age of onset was ≤3 years in five cases (13.5%). The patients revealed additional features including delayed walking, ataxia, dysphagia, dysarthria, dementia, ptosis, waddling gait, tremor, hearing loss, and abnormal visual evoked potential. Signs of ataxia were found in 26 patients (70.3%). In leg MRI analyses, various degrees of intramuscular fat infiltration were found. All compartments were evenly affected in CMT1F patients. The anterior and anterolateral compartments were affected in CMT2E, and the posterior compartment was affected in CMTDIG. Thus, NEFL‐related CMT patients showed phenotypic heterogeneities. This study's clinical, genetic, and neuroimaging results could be helpful in the evaluation of novel NEFL variants and differential diagnosis against other CMT subtypes. |
format | Online Article Text |
id | pubmed-8830812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88308122022-02-14 Phenotypic heterogeneity in patients with NEFL‐related Charcot–Marie–Tooth disease Kim, Hye Jin Kim, Sang Beom Kim, Hyun Su Kwon, Hye Mi Park, Jae Hong Lee, Ah Jin Lim, Si On Nam, Soo Hyun Hong, Young Bin Chung, Ki Wha Choi, Byung‐Ok Mol Genet Genomic Med Original Articles Charcot–Marie–Tooth disease (CMT) is the most common hereditary peripheral neuropathy. Mutations in the neurofilament light polypeptide (NEFL) gene produce diverse clinical phenotypes, including demyelinating (CMT1F), axonal (CMT2E), and intermediate (CMTDIG) neuropathies. From 2005 to 2020, 1,143 Korean CMT families underwent gene sequencing, and we investigated the clinical, genetic, and neuroimaging spectra of NEFL‐related CMT patients. Ten NEFL mutations in 17 families (1.49%) were identified, of which three (p.L312P, p.Y443N, and p.K467N) were novel. Eight de novo cases were identified at a rate of 0.47 based on a cosegregation analysis. The age of onset was ≤3 years in five cases (13.5%). The patients revealed additional features including delayed walking, ataxia, dysphagia, dysarthria, dementia, ptosis, waddling gait, tremor, hearing loss, and abnormal visual evoked potential. Signs of ataxia were found in 26 patients (70.3%). In leg MRI analyses, various degrees of intramuscular fat infiltration were found. All compartments were evenly affected in CMT1F patients. The anterior and anterolateral compartments were affected in CMT2E, and the posterior compartment was affected in CMTDIG. Thus, NEFL‐related CMT patients showed phenotypic heterogeneities. This study's clinical, genetic, and neuroimaging results could be helpful in the evaluation of novel NEFL variants and differential diagnosis against other CMT subtypes. John Wiley and Sons Inc. 2022-01-19 /pmc/articles/PMC8830812/ /pubmed/35044100 http://dx.doi.org/10.1002/mgg3.1870 Text en © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Kim, Hye Jin Kim, Sang Beom Kim, Hyun Su Kwon, Hye Mi Park, Jae Hong Lee, Ah Jin Lim, Si On Nam, Soo Hyun Hong, Young Bin Chung, Ki Wha Choi, Byung‐Ok Phenotypic heterogeneity in patients with NEFL‐related Charcot–Marie–Tooth disease |
title | Phenotypic heterogeneity in patients with NEFL‐related Charcot–Marie–Tooth disease |
title_full | Phenotypic heterogeneity in patients with NEFL‐related Charcot–Marie–Tooth disease |
title_fullStr | Phenotypic heterogeneity in patients with NEFL‐related Charcot–Marie–Tooth disease |
title_full_unstemmed | Phenotypic heterogeneity in patients with NEFL‐related Charcot–Marie–Tooth disease |
title_short | Phenotypic heterogeneity in patients with NEFL‐related Charcot–Marie–Tooth disease |
title_sort | phenotypic heterogeneity in patients with nefl‐related charcot–marie–tooth disease |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830812/ https://www.ncbi.nlm.nih.gov/pubmed/35044100 http://dx.doi.org/10.1002/mgg3.1870 |
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