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01-03-2016 | Original Communication

Clinical, neurophysiological and morphological study of dominant intermediate Charcot-Marie-Tooth type C neuropathy

Authors: Florian P. Thomas, Velina Guergueltcheva, Francisco A. A. Gondim, Ivailo Tournev, Chitharanjan V. Rao, Boryana Ishpekova, Laurence J. Kinsella, Yi Pan, Thomas J. Geller, Ivan Litvinenko, Peter De Jonghe, Steven S. Scherer, Albena Jordanova

Published in: Journal of Neurology | Issue 3/2016

Abstract

Dominant intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) was associated with mutations in the YARS gene, encoding tyrosyl-tRNA synthetase, in two large unrelated Bulgarian and US pedigrees and one sporadic case. Here for the first time we describe the clinical, neurophysiological and histopathological features, and phenotypic differences between these two DI-CMTC families. Twenty-one affected individuals from the US family and 27 from the Bulgarian family were evaluated. The mean age of onset in US subjects was 10.7 years in men and 7.3 years in women, while in the Bulgarian participants it was 18.2 years in men and 33.7 years in women. The course was slowly progressive. Extensor digitorum brevis atrophy was uniform. Atrophy and/or weakness of upper and lower limb muscles were found in over 50 % of the subjects. Nerve conduction studies (NCS) were abnormal in all US adults and five of six children and all Bulgarian patients except one asymptomatic 25-year-old man. Median motor NCS were in the range of 29.5–45.6 m/s in the US family and 24.7–57.8 m/s in the Bulgarian family. Sural sensory nerve action potentials were absent in 14/21 and 4/12 NCS from adult US and Bulgarian participants, respectively. Analysis of sural nerve biopsies from US patients revealed age-dependent morphological changes of axonal degeneration, absence of onion bulbs, and <10 % fibers with segmental remyelination. Our findings provide further insights into the diagnosis and pathology of intermediate CMT. They also extend the phenotypic spectrum of peripheral neuropathies associated with aminoacyl-tRNA synthetase mutations.

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Title: Clinical, neurophysiological and morphological study of dominant intermediate Charcot-Marie-Tooth type C neuropathy
Authors: Florian P. Thomas
Velina Guergueltcheva
Francisco A. A. Gondim
Ivailo Tournev
Chitharanjan V. Rao
Boryana Ishpekova
Laurence J. Kinsella
Yi Pan
Thomas J. Geller
Ivan Litvinenko
Peter De Jonghe
Steven S. Scherer
Albena Jordanova
Publication date: 01-03-2016
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 3/2016
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-015-7989-8

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Clinical, neurophysiological and morphological study of dominant intermediate Charcot-Marie-Tooth type C neuropathy

Abstract

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