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

Title
A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy
Authors
Hong, Young BinJoo, JaesoonHyun, Young SeKwak, GeonChoi, Yu-RiYeo, Ha KyungJwa, Dong HwanKim, Eun JaMo, Won MinNam, Soo HyunKim, Sung MinYoo, Jeong HyunKoo, HeasooPark, Hwan TaeChung, Ki WhaChoi, Byung-Ok
Ewha Authors
구혜수유정현
SCOPUS Author ID
구혜수scopus; 유정현scopus
Issue Date
2016
Journal Title
PLOS GENETICS
ISSN
1553-7404JCR Link
Citation
vol. 12, no. 2
Publisher
PUBLIC LIBRARY SCIENCE
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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.
DOI
10.1371/journal.pgen.1005829
Appears in Collections:
의과대학 > 의학과 > Journal papers
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