{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:15:35Z","timestamp":1791270935024,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,9,17]],"date-time":"2014-09-17T00:00:00Z","timestamp":1410912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Mutations in Charcot\u2013Marie\u2013Tooth disease (CMT) genes are the cause of rare familial forms of polyneuropathy. Whether allelic variability in CMT genes is also associated with common forms of polyneuropathy\u2014considered \u201cacquired\u201d in medical parlance\u2014is unknown. Chemotherapy\u2010induced peripheral neuropathy (CIPN) occurs commonly in cancer patients and is individually unpredictable. We used CIPN as a clinical model to investigate the association of non\u2010CMT polyneuropathy with CMT genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 269 neurologically asymptomatic cancer patients were enrolled in the clinical trial Alliance N08C1 to receive the neurotoxic drug paclitaxel, while undergoing prospective assessments for polyneuropathy. Forty\u2010nine CMT genes were analyzed by targeted massively parallel sequencing of genomic DNA from patient blood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 119 (of 269) patients were identified from the 2 ends of the polyneuropathy phenotype distribution: patients that were most and least susceptible to paclitaxel polyneuropathy. The CMT gene <jats:italic>PRX<\/jats:italic> was found to be deleteriously mutated in patients who were susceptible to CIPN but not in controls (<jats:italic>p<\/jats:italic>\u2009=\u20098 \u00d7 10<jats:sup>\u22123<\/jats:sup>). Genetic variation in another CMT gene, <jats:italic>ARHGEF10<\/jats:italic>, was highly significantly associated with CIPN (<jats:italic>p<\/jats:italic>\u2009=\u20095 \u00d7 10<jats:sup>\u22124<\/jats:sup>). Three nonsynonymous recurrent single nucleotide variants contributed to the <jats:italic>ARHGEF10<\/jats:italic> signal: rs9657362, rs2294039, and rs17683288. Of these, rs9657362 had the strongest effect (odds ratio\u2009=\u20094.8, <jats:italic>p<\/jats:italic>\u2009=\u20094 \u00d7 10<jats:sup>\u22124<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The results reveal an association of CMT gene allelic variability with susceptibility to CIPN. The findings raise the possibility that other acquired polyneuropathies may also be codetermined by genetic etiological factors, of which some may be related to genes already known to cause the phenotypically related Mendelian disorders of CMT. Ann Neurol 2014;76:727\u2013737<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24265","type":"journal-article","created":{"date-parts":[[2014,8,28]],"date-time":"2014-08-28T09:05:10Z","timestamp":1409216710000},"page":"727-737","source":"Crossref","is-referenced-by-count":73,"title":["Sequencing of <scp>C<\/scp>harcot\u2013<scp>M<\/scp>arie\u2013<scp>T<\/scp>ooth disease genes in a toxic polyneuropathy"],"prefix":"10.1002","volume":"76","author":[{"given":"Andreas S.","family":"Beutler","sequence":"first","affiliation":[{"name":"Department of Oncology Mayo Clinic Rochester MN"},{"name":"Cancer Center Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit A.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Oncology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Kanwar","sequence":"additional","affiliation":[{"name":"Department of Oncology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry M.","family":"Therneau","sequence":"additional","affiliation":[{"name":"Cancer Center Mayo Clinic Rochester MN"},{"name":"Division of Bioinformatics and Biostatistics Department of Health Sciences Research Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Qin","sequence":"additional","affiliation":[{"name":"Cancer Center Mayo Clinic Rochester MN"},{"name":"Division of Bioinformatics and Biostatistics Department of Health Sciences Research Mayo Clinic Rochester MN"},{"name":"Alliance for Clinical Trials in Oncology Statistics and Data Center Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela S.","family":"Banck","sequence":"additional","affiliation":[{"name":"Department of Oncology Mayo Clinic Rochester MN"},{"name":"Cancer Center Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh K.","family":"Boora","sequence":"additional","affiliation":[{"name":"Department of Oncology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn J.","family":"Ruddy","sequence":"additional","affiliation":[{"name":"Department of Oncology Mayo Clinic Rochester MN"},{"name":"Cancer Center Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Wu","sequence":"additional","affiliation":[{"name":"Genotyping Core Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regenia L.","family":"Smalley","sequence":"additional","affiliation":[{"name":"Genotyping Core Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie M.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Genotyping Core Mayo Clinic Rochester MN"},{"name":"Department of Laboratory Pathology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyet Anh","family":"Le\u2010Lindqwister","sequence":"additional","affiliation":[{"name":"Illinois Oncology Research Association Community Clinical Oncology Program Peoria IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Beyerlein","sequence":"additional","affiliation":[{"name":"Bioinformatik Technical University of Applied Sciences Wildau Wildau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary P.","family":"Schroth","sequence":"additional","affiliation":[{"name":"Illumina Hayward CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Windebank","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Z\u00fcchner","sequence":"additional","affiliation":[{"name":"John T. 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