{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T13:40:18Z","timestamp":1769348418414,"version":"3.49.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Charcot-Marie-Tooth type 4C (CMT4C) is a slowly progressive, autosomal recessive, sensorimotor polyneuropathy characterized by demyelination and distinct clinical features, including cranial nerve involvement. CMT4C is associated with pathogenic mutations in the SH3TC2 gene.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A patient presenting with gait instability due to demyelinating polyneuropathy and refractory trigeminal neuralgia underwent comprehensive evaluation. Nerve conduction studies, magnetic resonance imaging (MRI) of the brain, cervical spine, and thoracic spine, lumbar puncture, and genetic test through next generation sequencing were performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The genetic test found an Arg1109Stop mutation in the SH3TC2 gene, associated with demyelinating polyneuropathy and cranial neuropathy. Interestingly, brain MRI showed multiple, nonenhancing white matter hyperintensities. This is the first case of CMT4C associated with white matter lesions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Any patient with slowly progressive peripheral nervous system symptoms and disproportionally abnormal nerve conduction study findings should be tested for an inherited polyneuropathy and brain imaging for screening of possible central nervous system involvement should be performed. Further investigation is needed to elucidate the pathogenetic basis of CMT4C and a possible association with white matter lesions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/labmed\/lmae081","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T22:05:27Z","timestamp":1726869927000},"page":"195-198","source":"Crossref","is-referenced-by-count":1,"title":["Trigeminal neuralgia, demyelinating polyneuropathy, and central nervous system involvement in a patient with an <i>SH3TC2<\/i> mutation"],"prefix":"10.1093","volume":"56","author":[{"given":"Alexandros","family":"Giannakis","sequence":"first","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Ioannina , Ioannina ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gkirai","family":"Chamko","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Ioannina , Ioannina ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Sarmas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Ioannina , Ioannina ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Pepe","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Patras , Patras ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Sidiropoulos","sequence":"additional","affiliation":[{"name":"Department of Neurology, Michigan State University , East Lansing, MI ,","place":["US"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Spiridon","family":"Konitsiotis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Ioannina , Ioannina ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"issue":"3","key":"2025031011215271800_CIT0001","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/jns.12175","article-title":"Screening for SH3TC2 gene mutations in a series of demyelinating recessive Charcot-Marie-Tooth disease (CMT4)","volume":"21","author":"Piscosquito","year":"2016","journal-title":"J Peripher Nerv"},{"issue":"5","key":"2025031011215271800_CIT0002","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1002\/mus.25981","article-title":"Charcot\u2013Marie\u2013Tooth disease type 4C: novel mutations, clinical presentations, and diagnostic challenges","volume":"57","author":"Jerath","year":"2018","journal-title":"Muscle Nerve."},{"issue":"4","key":"2025031011215271800_CIT0003","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1111\/j.1750-3639.1992.tb00710.x","article-title":"Molecular genetics and neuropathology of Charcot-Marie-Tooth disease type 1A","volume":"2","author":"Lupski","year":"1992","journal-title":"Brain Pathol."},{"issue":"5","key":"2025031011215271800_CIT0004","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1212\/CON.0000000000000927","article-title":"Charcot-Marie-Tooth disease and other hereditary neuropathies","volume":"26","author":"Klein","year":"2020","journal-title":"Continuum."},{"issue":"1","key":"2025031011215271800_CIT0005","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/jns.12305","article-title":"Mutational screening of the SH3TC2 gene in Greek patients with suspected demyelinating recessive Charcot-Marie-Tooth disease reveals a varied and unusual phenotypic spectrum","volume":"24","author":"Kontogeorgiou","year":"2019","journal-title":"J Peripher Nerv Syst."},{"issue":"9","key":"2025031011215271800_CIT0006","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1038\/s10038-019-0636-y","article-title":"Compound heterozygous mutations of SH3TC2 in Charcot\u2013Marie\u2013Tooth disease type 4C patients","volume":"64","author":"Lee","year":"2019","journal-title":"J Hum Genet."},{"issue":"10","key":"2025031011215271800_CIT0007","doi-asserted-by":"publisher","first-page":"2234","DOI":"10.1016\/j.clineuro.2013.07.010","article-title":"Charcot-Marie-Tooth and trigeminal neuralgia","volume":"115","author":"Wong","year":"2013","journal-title":"Clin Neurol Neurosurg."},{"issue":"3","key":"2025031011215271800_CIT0008","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/s10038-017-0388-5","article-title":"Clinical and mutational spectrum of Japanese patients with recessive variants in SH3TC2","volume":"63","author":"Yuan","year":"2018","journal-title":"J Hum Genet."},{"issue":"5","key":"2025031011215271800_CIT0009","doi-asserted-by":"publisher","first-page":"940","DOI":"10.4103\/0028-3886.388101","article-title":"Characterisation of patients with SH3TC2 associated neuropathy in an Indian cohort","volume":"71","author":"Nagappa","year":"2023","journal-title":"Neurol India."},{"key":"2025031011215271800_CIT0010","doi-asserted-by":"publisher","first-page":"682050","DOI":"10.3389\/fgene.2021.682050","article-title":"Cohort analysis of 67 Charcot-Marie-Tooth Italian patients: identification of new mutations and broadening of phenotype expression produced by rare variants","volume":"12","author":"Ferese","year":"2021","journal-title":"Front Genet."},{"issue":"1","key":"2025031011215271800_CIT0011","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1111\/ene.14514","article-title":"Inherited neuropathies with predominant upper limb involvement: genetic heterogeneity and overlapping pathologies","volume":"28","author":"McMacken","year":"2021","journal-title":"Eur J Neurol."},{"issue":"9","key":"2025031011215271800_CIT0012","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1038\/mp.2015.204","article-title":"Common variants on 17q25 and gene\u2013gene interactions conferring risk of schizophrenia in Han Chinese population and regulating gene expressions in human brain","volume":"21","author":"Guan","year":"2016","journal-title":"Mol Psychiatry."},{"issue":"6","key":"2025031011215271800_CIT0013","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1002\/ajmg.b.30903","article-title":"Characterization of a de novo translocation t(5;18)(q33.1;q12.1) in an autistic boy identifies a breakpoint close to SH3TC2, ADRB2, and HTR4 on 5q, and within the desmocollin gene cluster on 18q","volume":"150B","author":"Vincent","year":"2009","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"issue":"Pt 8","key":"2025031011215271800_CIT0014","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.1093\/brain\/awq168","article-title":"SH3TC2, a protein mutant in Charcot-Marie-Tooth neuropathy, links peripheral nerve myelination to endosomal recycling","volume":"133","author":"Stendel","year":"2010","journal-title":"Brain."},{"issue":"5","key":"2025031011215271800_CIT0015","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.ajhg.2017.09.015","article-title":"Recurrent de novo mutations disturbing the GTP\/GDP binding pocket of RAB11B cause intellectual disability and a distinctive brain phenotype","volume":"101","author":"Lamers","year":"2017","journal-title":"Am J Hum Genet."},{"issue":"4","key":"2025031011215271800_CIT0016","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1093\/hmg\/ddu521","article-title":"Rab11 modulates \u03b1-synuclein-mediated defects in synaptic transmission and behaviour","volume":"24","author":"Breda","year":"2015","journal-title":"Hum Mol Genet."},{"key":"2025031011215271800_CIT0017","doi-asserted-by":"publisher","first-page":"146572","DOI":"10.1016\/j.brainres.2019.146572","article-title":"Gene therapy approaches targeting Schwann cells for demyelinating neuropathies","volume":"1728","author":"Sargiannidou","year":"2020","journal-title":"Brain Res."},{"issue":"11","key":"2025031011215271800_CIT0018","doi-asserted-by":"publisher","first-page":"6048","DOI":"10.3390\/ijms22116048","article-title":"Emerging therapies for Charcot-Marie-Tooth inherited neuropathies","volume":"22","author":"Stavrou","year":"2021","journal-title":"Int J Mol Sci ."},{"issue":"9","key":"2025031011215271800_CIT0019","doi-asserted-by":"publisher","first-page":"3826","DOI":"10.1093\/brain\/awad095","article-title":"Neuropathy due to bi-allelic SH3TC2 variants: genotype-phenotype correlation and natural history","volume":"146","author":"Rehbein","year":"2023","journal-title":"Brain."},{"issue":"11","key":"2025031011215271800_CIT0020","doi-asserted-by":"publisher","first-page":"3290","DOI":"10.1016\/j.ymthe.2023.08.020","article-title":"AAV9-mediated SH3TC2 gene replacement therapy targeted to Schwann cells for the treatment of CMT4C","volume":"31","author":"Georgiou","year":"2023","journal-title":"Mol Ther."}],"container-title":["Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/labmed\/article-pdf\/56\/2\/195\/59215221\/lmae081.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/labmed\/article-pdf\/56\/2\/195\/59215221\/lmae081.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T11:22:02Z","timestamp":1741605722000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/labmed\/article\/56\/2\/195\/7762940"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,20]]},"references-count":20,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,9,20]]},"published-print":{"date-parts":[[2025,3,10]]}},"URL":"https:\/\/doi.org\/10.1093\/labmed\/lmae081","relation":{},"ISSN":["0007-5027","1943-7730"],"issn-type":[{"value":"0007-5027","type":"print"},{"value":"1943-7730","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2024,9,20]]}}}