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Clinical and genetic diversities of Charcot‐Marie‐Tooth disease with MFN2 mutations in a large case study
Charcot‐Marie‐Tooth disease (CMT) constitutes a heterogeneous group affecting motor and sensory neurons in the peripheral nervous system. MFN2 mutations are the most common cause of axonal CMT. We describe the clinical and mutational spectra of CMT patients harboring MFN2 mutations in Japan. We anal...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wiley Periodicals, Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697682/ https://www.ncbi.nlm.nih.gov/pubmed/28660751 http://dx.doi.org/10.1111/jns.12228 |
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author | Ando, Masahiro Hashiguchi, Akihiro Okamoto, Yuji Yoshimura, Akiko Hiramatsu, Yu Yuan, Junhui Higuchi, Yujiro Mitsui, Jun Ishiura, Hiroyuki Umemura, Ayako Maruyama, Koichi Matsushige, Takeshi Morishita, Shinichi Nakagawa, Masanori Tsuji, Shoji Takashima, Hiroshi |
author_facet | Ando, Masahiro Hashiguchi, Akihiro Okamoto, Yuji Yoshimura, Akiko Hiramatsu, Yu Yuan, Junhui Higuchi, Yujiro Mitsui, Jun Ishiura, Hiroyuki Umemura, Ayako Maruyama, Koichi Matsushige, Takeshi Morishita, Shinichi Nakagawa, Masanori Tsuji, Shoji Takashima, Hiroshi |
author_sort | Ando, Masahiro |
collection | PubMed |
description | Charcot‐Marie‐Tooth disease (CMT) constitutes a heterogeneous group affecting motor and sensory neurons in the peripheral nervous system. MFN2 mutations are the most common cause of axonal CMT. We describe the clinical and mutational spectra of CMT patients harboring MFN2 mutations in Japan. We analyzed 1,334 unrelated patients with clinically suspected CMT referred by neurological and neuropediatric departments throughout Japan. We conducted mutation screening using a DNA microarray, targeted resequencing, and whole‐exome sequencing. We identified pathogenic or likely pathogenic MFN2 variants from 79 CMT patients, comprising 44 heterozygous and 1 compound heterozygous variants. A total of 15 novel variants were detected. An autosomal dominant family history was determined in 43 cases, and the remaining 36 cases were reported as sporadic with no family history. The mean onset age of CMT in these patients was 12 ± 14 (range 0–59) years. We observed neuropathic symptoms in all patients. Some had optic atrophy, vocal cord paralysis, or spasticity. We detected a compound heterozygous MFN2 mutation in a patient with a severe phenotype and the co‐occurrence of MFN2 and PMP22 mutations in a patient with an uncommon phenotype. MFN2 is the most frequent causative gene of CMT2 in Japan. We present 15 novel variants and broad clinical and mutational spectra of Japanese MFN2‐related CMT patients. Regardless of the onset age and inheritance pattern, MFN2 gene analysis should be performed. Combinations of causative genes should be considered to explain the phenotypic diversity. |
format | Online Article Text |
id | pubmed-5697682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Wiley Periodicals, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56976822017-11-28 Clinical and genetic diversities of Charcot‐Marie‐Tooth disease with MFN2 mutations in a large case study Ando, Masahiro Hashiguchi, Akihiro Okamoto, Yuji Yoshimura, Akiko Hiramatsu, Yu Yuan, Junhui Higuchi, Yujiro Mitsui, Jun Ishiura, Hiroyuki Umemura, Ayako Maruyama, Koichi Matsushige, Takeshi Morishita, Shinichi Nakagawa, Masanori Tsuji, Shoji Takashima, Hiroshi J Peripher Nerv Syst Research Reports Charcot‐Marie‐Tooth disease (CMT) constitutes a heterogeneous group affecting motor and sensory neurons in the peripheral nervous system. MFN2 mutations are the most common cause of axonal CMT. We describe the clinical and mutational spectra of CMT patients harboring MFN2 mutations in Japan. We analyzed 1,334 unrelated patients with clinically suspected CMT referred by neurological and neuropediatric departments throughout Japan. We conducted mutation screening using a DNA microarray, targeted resequencing, and whole‐exome sequencing. We identified pathogenic or likely pathogenic MFN2 variants from 79 CMT patients, comprising 44 heterozygous and 1 compound heterozygous variants. A total of 15 novel variants were detected. An autosomal dominant family history was determined in 43 cases, and the remaining 36 cases were reported as sporadic with no family history. The mean onset age of CMT in these patients was 12 ± 14 (range 0–59) years. We observed neuropathic symptoms in all patients. Some had optic atrophy, vocal cord paralysis, or spasticity. We detected a compound heterozygous MFN2 mutation in a patient with a severe phenotype and the co‐occurrence of MFN2 and PMP22 mutations in a patient with an uncommon phenotype. MFN2 is the most frequent causative gene of CMT2 in Japan. We present 15 novel variants and broad clinical and mutational spectra of Japanese MFN2‐related CMT patients. Regardless of the onset age and inheritance pattern, MFN2 gene analysis should be performed. Combinations of causative genes should be considered to explain the phenotypic diversity. Wiley Periodicals, Inc. 2017-07-30 2017-09 /pmc/articles/PMC5697682/ /pubmed/28660751 http://dx.doi.org/10.1111/jns.12228 Text en © 2017 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Reports Ando, Masahiro Hashiguchi, Akihiro Okamoto, Yuji Yoshimura, Akiko Hiramatsu, Yu Yuan, Junhui Higuchi, Yujiro Mitsui, Jun Ishiura, Hiroyuki Umemura, Ayako Maruyama, Koichi Matsushige, Takeshi Morishita, Shinichi Nakagawa, Masanori Tsuji, Shoji Takashima, Hiroshi Clinical and genetic diversities of Charcot‐Marie‐Tooth disease with MFN2 mutations in a large case study |
title | Clinical and genetic diversities of Charcot‐Marie‐Tooth disease with MFN2 mutations in a large case study |
title_full | Clinical and genetic diversities of Charcot‐Marie‐Tooth disease with MFN2 mutations in a large case study |
title_fullStr | Clinical and genetic diversities of Charcot‐Marie‐Tooth disease with MFN2 mutations in a large case study |
title_full_unstemmed | Clinical and genetic diversities of Charcot‐Marie‐Tooth disease with MFN2 mutations in a large case study |
title_short | Clinical and genetic diversities of Charcot‐Marie‐Tooth disease with MFN2 mutations in a large case study |
title_sort | clinical and genetic diversities of charcot‐marie‐tooth disease with mfn2 mutations in a large case study |
topic | Research Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697682/ https://www.ncbi.nlm.nih.gov/pubmed/28660751 http://dx.doi.org/10.1111/jns.12228 |
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