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A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy

Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical fe...

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Autores principales: Hong, Young Bin, Joo, Jaesoon, Hyun, Young Se, Kwak, Geon, Choi, Yu-Ri, Yeo, Ha Kyung, Jwa, Dong Hwan, Kim, Eun Ja, Mo, Won Min, Nam, Soo Hyun, Kim, Sung Min, Yoo, Jeong Hyun, Koo, Heasoo, Park, Hwan Tae, Chung, Ki Wha, Choi, Byung-Ok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735456/
https://www.ncbi.nlm.nih.gov/pubmed/26828946
http://dx.doi.org/10.1371/journal.pgen.1005829
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author Hong, Young Bin
Joo, Jaesoon
Hyun, Young Se
Kwak, Geon
Choi, Yu-Ri
Yeo, Ha Kyung
Jwa, Dong Hwan
Kim, Eun Ja
Mo, Won Min
Nam, Soo Hyun
Kim, Sung Min
Yoo, Jeong Hyun
Koo, Heasoo
Park, Hwan Tae
Chung, Ki Wha
Choi, Byung-Ok
author_facet Hong, Young Bin
Joo, Jaesoon
Hyun, Young Se
Kwak, Geon
Choi, Yu-Ri
Yeo, Ha Kyung
Jwa, Dong Hwan
Kim, Eun Ja
Mo, Won Min
Nam, Soo Hyun
Kim, Sung Min
Yoo, Jeong Hyun
Koo, Heasoo
Park, Hwan Tae
Chung, Ki Wha
Choi, Byung-Ok
author_sort Hong, Young Bin
collection PubMed
description Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical features. The age at onset was the first to second decades and muscle atrophy started in the distal portion of the leg. Predominant fatty replacement in the anterior and lateral compartment was similar to that in CMT1A caused by PMP22 duplication. Sural nerve biopsy showed onion bulbs and degenerating fibers with various myelin abnormalities. The relevance of PMP2 mutation as a genetic cause of dominant CMT1 was assessed using transgenic mouse models. Transgenic mice expressing wild type or mutant (p.I43N) PMP2 exhibited abnormal motor function. Electrophysiological data revealed that both mice had reduced motor nerve conduction velocities (MNCV). Electron microscopy revealed that demyelinating fibers and internodal lengths were shortened in both transgenic mice. These data imply that overexpression of wild type as well as mutant PMP2 also causes the CMT1 phenotype, which has been documented in the PMP22. This report might expand the genetic and clinical features of CMT and a further mechanism study will enhance our understanding of PMP2-associated peripheral neuropathy.
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spelling pubmed-47354562016-02-04 A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy Hong, Young Bin Joo, Jaesoon Hyun, Young Se Kwak, Geon Choi, Yu-Ri Yeo, Ha Kyung Jwa, Dong Hwan Kim, Eun Ja Mo, Won Min Nam, Soo Hyun Kim, Sung Min Yoo, Jeong Hyun Koo, Heasoo Park, Hwan Tae Chung, Ki Wha Choi, Byung-Ok PLoS Genet Research Article Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical features. The age at onset was the first to second decades and muscle atrophy started in the distal portion of the leg. Predominant fatty replacement in the anterior and lateral compartment was similar to that in CMT1A caused by PMP22 duplication. Sural nerve biopsy showed onion bulbs and degenerating fibers with various myelin abnormalities. The relevance of PMP2 mutation as a genetic cause of dominant CMT1 was assessed using transgenic mouse models. Transgenic mice expressing wild type or mutant (p.I43N) PMP2 exhibited abnormal motor function. Electrophysiological data revealed that both mice had reduced motor nerve conduction velocities (MNCV). Electron microscopy revealed that demyelinating fibers and internodal lengths were shortened in both transgenic mice. These data imply that overexpression of wild type as well as mutant PMP2 also causes the CMT1 phenotype, which has been documented in the PMP22. This report might expand the genetic and clinical features of CMT and a further mechanism study will enhance our understanding of PMP2-associated peripheral neuropathy. Public Library of Science 2016-02-01 /pmc/articles/PMC4735456/ /pubmed/26828946 http://dx.doi.org/10.1371/journal.pgen.1005829 Text en © 2016 Hong et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hong, Young Bin
Joo, Jaesoon
Hyun, Young Se
Kwak, Geon
Choi, Yu-Ri
Yeo, Ha Kyung
Jwa, Dong Hwan
Kim, Eun Ja
Mo, Won Min
Nam, Soo Hyun
Kim, Sung Min
Yoo, Jeong Hyun
Koo, Heasoo
Park, Hwan Tae
Chung, Ki Wha
Choi, Byung-Ok
A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy
title A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy
title_full A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy
title_fullStr A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy
title_full_unstemmed A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy
title_short A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy
title_sort mutation in pmp2 causes dominant demyelinating charcot-marie-tooth neuropathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735456/
https://www.ncbi.nlm.nih.gov/pubmed/26828946
http://dx.doi.org/10.1371/journal.pgen.1005829
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