{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:49:50Z","timestamp":1790603390031,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"German Ministry of Education and Research","award":["01GM1511F"],"award-info":[{"award-number":["01GM1511F"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Charcot\u2013Marie\u2013Tooth disease type 1A, caused by a duplication of the gene peripheral myelin protein 22\u2009kDa, is the most frequent subtype of hereditary peripheral neuropathy with an estimated prevalence of 1:5000. Patients suffer from sensory deficits, muscle weakness and foot deformities. There is no treatment approved for this disease. Outcome measures in clinical trials were based mainly on clinical features but did not evaluate the actual nerve damage. In our case\u2013control study, we aimed to provide objective and reproducible outcome measures for future clinical trials. We collected skin samples from 48 patients with Charcot\u2013Marie\u2013Tooth type 1A, 7 patients with chronic inflammatory demyelinating polyneuropathy, 16 patients with small fibre neuropathy and 45 healthy controls. To analyse skin innervation, 40-\u00b5m cryosections of glabrous skin taken from the lateral index finger were double-labelled by immunofluorescence. The disease severity of patients with Charcot\u2013Marie\u2013Tooth type 1A was assessed by the Charcot\u2013Marie\u2013Tooth neuropathy version 2 score, which ranged from 3 (mild) to 27 (severe) and correlated with age (P\u2009&amp;lt;\u20090.01, R\u2009=\u20090.4). Intraepidermal nerve fibre density was reduced in patients with Charcot\u2013Marie\u2013Tooth type 1A compared with the healthy control group (P\u2009&amp;lt;\u20090.01) and negatively correlated with disease severity (P\u2009&amp;lt;\u20090.05, R = \u22120.293). Meissner corpuscle (MC) density correlated negatively with age in patients with Charcot\u2013Marie\u2013Tooth type 1A (P\u2009&amp;lt;\u20090.01, R = \u22120.45) but not in healthy controls (P\u2009=\u20090.07, R\u2009=\u20090.28). The density of Merkel cells was reduced in patients with Charcot\u2013Marie\u2013Tooth type 1A compared with healthy controls (P\u2009&amp;lt;\u20090.05). Furthermore, in patients with Charcot\u2013Marie\u2013Tooth type 1A, the fraction of denervated Merkel cells was highly increased and correlated with age (P\u2009&amp;lt;\u20090.05, R\u2009=\u20090.37). Analysis of nodes of Ranvier revealed shortened paranodes and a reduced fraction of long nodes in patients compared with healthy controls (both P\u2009&amp;lt;\u20090.001). Langerhans cell density was increased in chronic inflammatory demyelinating polyneuropathy, but not different in Charcot\u2013Marie\u2013Tooth type 1A compared with healthy controls. Our data suggest that intraepidermal nerve fibre density might be used as an outcome measure in Charcot\u2013Marie\u2013Tooth type 1A disease, as it correlates with disease severity. The densities of Meissner corpuscles and Merkel cells might be an additional tool for the evaluation of the disease progression. Analysis of follow-up biopsies will clarify the effects of Charcot\u2013Marie\u2013Tooth type 1A disease progression on cutaneous innervation.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaa012","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T14:03:36Z","timestamp":1581516216000},"source":"Crossref","is-referenced-by-count":19,"title":["Intraepidermal nerve fibre density as biomarker in Charcot\u2013Marie\u2013Tooth disease type 1A"],"prefix":"10.1093","volume":"2","author":[{"given":"Beate","family":"Hartmannsberger","sequence":"first","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Doppler","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3198-7269","authenticated-orcid":false,"given":"Julia","family":"Stauber","sequence":"additional","affiliation":[{"name":"Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Schlotter-Weigel","sequence":"additional","affiliation":[{"name":"Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Young","sequence":"additional","affiliation":[{"name":"Medical Park Bad Feilnbach Reithofpark, Department of Neurology, 83075 Bad Feilnbach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W","family":"Sereda","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology, University Medical Center G\u00f6ttingen (UMG), 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sommer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,12]]},"reference":[{"key":"2020081109065381700_fcaa012-B1","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.neuron.2013.07.051","article-title":"The sensory neurons of touch","volume":"79","author":"Abraira","year":"2013","journal-title":"Neuron"},{"key":"2020081109065381700_fcaa012-B2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0896-6273(00)80047-1","article-title":"Specific subtypes of cutaneous mechanoreceptors require neurotrophin-3 following peripheral target 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