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MicroRNAs act as repressors on post-transcriptional regulation of gene expression and in rodent models of CMT1A, overexpression of one such microRNA (miR-29a) has been shown to reduce the PMP22 transcript and protein level.<\/jats:p>\n               <jats:p>Here we present genomic and functional evidence, for the first time in a human CNV-associated phenotype, of the 3\u2032 untranslated region (3\u2032-UTR)-mediated role of microRNA repression on gene expression.<\/jats:p>\n               <jats:p>The proband of the family presented with an early-onset, severe sensorimotor demyelinating neuropathy and harboured a novel de novo deletion in the PMP22 3\u2032-UTR. The deletion is predicted to include the miR-29a seed binding site and transcript analysis of dermal myelinated nerve fibres using a novel platform, revealed a marked increase in PMP22 transcript levels. Functional evidence from Schwann cell lines harbouring the wild-type and mutant 3\u2032-UTR showed significantly increased reporter assay activity in the latter, which was not ameliorated by overexpression of a miR-29a mimic.<\/jats:p>\n               <jats:p>This shows the importance of miR-29a in regulating PMP22 expression and opens an avenue for therapeutic drug development.<\/jats:p>","DOI":"10.1093\/brain\/awad203","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T06:54:31Z","timestamp":1687244071000},"page":"4025-4032","source":"Crossref","is-referenced-by-count":11,"title":["Post-transcriptional microRNA repression of <i>PMP22<\/i> dose in severe Charcot-Marie-Tooth disease type 1"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0511-6515","authenticated-orcid":false,"given":"Menelaos","family":"Pipis","sequence":"first","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of 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UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M","family":"Polke","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariola","family":"Skorupinska","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Blake","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology , London WC1N 3BG , UK"},{"name":"Department of Clinical Neurophysiology, Norfolk and Norwich University Hospital , Norwich NR4 7UY , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander M","family":"Rossor","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J","family":"Moran","sequence":"additional","affiliation":[{"name":"Waisman Center and Department of Comparative Biosciences, University of Wisconsin , Madison, WI 53706 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinki","family":"Munot","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, NIHR Biomedical Research Centre at UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital , London WC1N 1EH , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, NIHR Biomedical Research Centre at UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital , London WC1N 1EH , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matilde","family":"Laura","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-7921","authenticated-orcid":false,"given":"John","family":"Svaren","sequence":"additional","affiliation":[{"name":"Waisman Center and Department of Comparative Biosciences, University of Wisconsin , Madison, WI 53706 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0686-905X","authenticated-orcid":false,"given":"Mary M","family":"Reilly","sequence":"additional","affiliation":[{"name":"Centre for 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