TY - JOUR
T1 - Cross-sectional analysis of a large cohort with X-linked Charcot-Marie-Tooth disease (CMTX1)
AU - Panosyan, Francis B.
AU - Laura, Matilde
AU - Rossor, Alexander M.
AU - Pisciotta, Chiara
AU - Piscosquito, Giuseppe
AU - Burns, Joshua
AU - Li, Jun
AU - Yum, Sabrina W.
AU - Lewis, Richard A.
AU - Day, John
AU - Horvath, Rita
AU - Herrmann, David N.
AU - Shy, Michael E.
AU - Pareyson, Davide
AU - Reilly, Mary M.
AU - Scherer, Steven S.
N1 - Funding Information:
From the Department of Neurology (F.B.P., D.N.H.), University of Rochester Medical Center, NY; MRC Centre for Neuromuscular Diseases (M.L., A.M.R., M.M.R.), UCL Institute of Neurology, UK; Department of Neurology (C.P., D.P.), Carlo Besta Neurological Institute, Milan, Italy; Department of Neurosciences (G.P.), Institute of Telese Terme (BN), Italy; Children’s Hospital at Westmead (J.B.), University of Sydney, Australia; Department of Neurology (J.L.), Vanderbilt University, Nashville, TN; Neuromuscular Program (S.W.Y.), Children’s Hospital of Philadelphia, PA; Department of Neurology (R.A.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (J.D.), Stanford University, CA; Institute of Genetic Medicine (R.H.), Newcastle University, UK; Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics; and Department of Neurology (S.S.S.), University of Pennsylvania, Philadelphia. Coinvestigators are listed at Neurology.org. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was funded by Wellcome Trust. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Funding Information:
This study was funded through the INC (U54NS065712), which is a part of the NCATS Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR), NCATS, funded through a collaboration between NCATS and the NINDS. The work was also supported by the funding from the Muscular Dystrophy Association (MDA) and Charcot-Marie-Tooth Association. Some of this work was undertaken at University College London Hospitals/University College London, UK, which received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centre’s funding scheme.
Funding Information:
F.B. Panosyan is funded by the Inherited Neuropathies Consortium Fellowship Training program. M. Laura reports no disclosures relevant to the manuscript. A.M. Rossor is funded by a Wellcome Trust Postdoctoral Fellowship for Clinicians (110043/Z/15/Z). C. Pisciotta, G. Piscosquito, J. Burns, J. Li, S.W. Yum, R.A. Lewis, and J. Day report no disclosures relevant to the manuscript. R. Horvath is a Wellcome Trust Investigator (109915/Z/15/Z) and receives support from the Medical Research Council (UK) (MR/N025431/ 1) and the European Research Council (309548). D.N. Herrmann, M.E. Shy, D. Pareyson, M.M. Reilly, and S.S. Scherer report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
Publisher Copyright:
Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2017/8/29
Y1 - 2017/8/29
N2 - Objective: To extend the phenotypic description of Charcot-Marie-Tooth disease (CMTX1) and to draw new genotype-phenotype relationships. Methods: Mutations in GJB1 cause the main X-linked form of CMTX (CMTX1). We report cross-sectional data from 160 patients (from 120 different families, with 89 different mutations) seen at the Inherited Neuropathies Consortium centers. Results: We evaluated 87 males who had a mean age of 41 years (range 10-78 years) and 73 females who had a mean age of 46 years (range 15-84 years). Sensory-motor polyneuropathy affects both sexes, more severely in males than in females, and there was a strong correlation between age and disease burden in males but not in females. Compared with females, males had more severe reduction in motor and sensory neurophysiology parameters. In contrast to females, the radial nerve sensory response in older males tended to be more severely affected compared with younger males. Median and ulnar nerve motor amplitudes were also more severely affected in older males, whereas ulnar nerve motor potentials tended to be more affected in older females. Conversely, there were no statistical differences between the sexes in other features of the disease, such as problems with balance and hand dexterity. Conclusions: In the absence of a phenotypic correlation with specific GJB1 mutations, sex-specific distinctions and clinically relevant attributes need to be incorporated into the measurements for clinical trials in people with CMTX1. ClinicalTrials.gov identifier: NCT01193075.
AB - Objective: To extend the phenotypic description of Charcot-Marie-Tooth disease (CMTX1) and to draw new genotype-phenotype relationships. Methods: Mutations in GJB1 cause the main X-linked form of CMTX (CMTX1). We report cross-sectional data from 160 patients (from 120 different families, with 89 different mutations) seen at the Inherited Neuropathies Consortium centers. Results: We evaluated 87 males who had a mean age of 41 years (range 10-78 years) and 73 females who had a mean age of 46 years (range 15-84 years). Sensory-motor polyneuropathy affects both sexes, more severely in males than in females, and there was a strong correlation between age and disease burden in males but not in females. Compared with females, males had more severe reduction in motor and sensory neurophysiology parameters. In contrast to females, the radial nerve sensory response in older males tended to be more severely affected compared with younger males. Median and ulnar nerve motor amplitudes were also more severely affected in older males, whereas ulnar nerve motor potentials tended to be more affected in older females. Conversely, there were no statistical differences between the sexes in other features of the disease, such as problems with balance and hand dexterity. Conclusions: In the absence of a phenotypic correlation with specific GJB1 mutations, sex-specific distinctions and clinically relevant attributes need to be incorporated into the measurements for clinical trials in people with CMTX1. ClinicalTrials.gov identifier: NCT01193075.
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U2 - 10.1212/WNL.0000000000004296
DO - 10.1212/WNL.0000000000004296
M3 - Article
C2 - 28768847
AN - SCOPUS:85028503158
VL - 89
SP - 927
EP - 935
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 9
ER -