{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:12:01Z","timestamp":1790237521022,"version":"4.1.0"},"reference-count":22,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011724","name":"MDUK","doi-asserted-by":"crossref","award":["24GRO-PG24-0719"],"award-info":[{"award-number":["24GRO-PG24-0719"]}],"id":[{"id":"10.13039\/100011724","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100002243","name":"National Ataxia Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002243","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AFM-Telethon","award":["28813"],"award-info":[{"award-number":["28813"]}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["101165557"],"award-info":[{"award-number":["101165557"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002721","name":"Charcot-Marie-Tooth Association","doi-asserted-by":"publisher","award":["SR-202504 Cortese UCL VUS"],"award-info":[{"award-number":["SR-202504 Cortese UCL VUS"]}],"id":[{"id":"10.13039\/100002721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T001712\/1"],"award-info":[{"award-number":["MR\/T001712\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2025,6,11]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"\n Background<\/jats:title>\n \n CGG expansions in\n NOTCH2NLC<\/jats:italic>\n and\n LRP12<\/jats:italic>\n were recently identified as a cause of Charcot-Marie-Tooth disease (CMT) in 1.2%\u201310.6% of genetically undiagnosed patients in China, Taiwan and Japan. However, their relevance in CMT patients of different ethnic origin is still unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Here, we leveraged short-read whole genome sequencing data from the 100\u2009000 Genomes Project to investigate the presence and frequency of CGG expansions in\n NOTCH2NLC<\/jats:italic>\n ,\n LRP12<\/jats:italic>\n and additional genes associated with oculopharyngodistal myopathy (OPDM), in 560 genetically unsolved patients diagnosed with CMT and 32\u2009509 non-neurological controls.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Repeat expansions in\n NOTCH2NLC<\/jats:italic>\n ,\n LRP12<\/jats:italic>\n ,\n RILPL1<\/jats:italic>\n ,\n NUTM2B-AS1<\/jats:italic>\n and\n ABCD3<\/jats:italic>\n were absent from 560 genetically unsolved patients with CMT, mostly of Northern European ancestry. One patient of African ancestry carried an expanded allele in\n GIPC1<\/jats:italic>\n , below the reported pathogenic threshold. However, rare expansions in this gene, as well as in\n NOTCH2NLC<\/jats:italic>\n ,\n NUTM2B-AS1<\/jats:italic>\n and\n ABCD3<\/jats:italic>\n , were also detected in controls (\u22640.05%). The distribution of repeat size at these loci varied significantly across different ethnicities, with larger non-pathogenic intermediate alleles of\n NOTCH2NLC<\/jats:italic>\n and\n LRP12<\/jats:italic>\n typically observed in East Asians.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n CGG expansions in\n NOTCH2NLC<\/jats:italic>\n ,\n LRP12<\/jats:italic>\n and other OPDM-associated genes do not appear to be a relevant cause of CMT in the UK. The larger size of non-pathogenic intermediate alleles of\n NOTCH2NLC<\/jats:italic>\n and\n LRP12<\/jats:italic>\n in East Asians could explain their ancestry-specific propensity to further expand into the full pathogenic range.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/jnnp-2025-336590","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T21:40:31Z","timestamp":1752270031000},"page":"479-482","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["CGG repeat expansions in Charcot-Marie-Tooth disease: insights from the 100 000 Genomes Project"],"prefix":"10.1136","volume":"97","author":[{"given":"Alessandro","family":"Bertini","sequence":"first","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"},{"name":"Unit of Rare Neurological Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Facchini","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Quartesan","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-0550","authenticated-orcid":false,"given":"Riccardo","family":"Curr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Parolin","family":"Schnekenberg","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Dominik","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"},{"name":"Clinical Hospital of Ribeir\u00e3o Preto, Department of Neurosciences and Behaviour Sciences, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Ferullo","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"},{"name":"Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Tucci","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-7777","authenticated-orcid":false,"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0686-905X","authenticated-orcid":false,"given":"Mary M","family":"Reilly","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2208-5311","authenticated-orcid":false,"given":"Andrea","family":"Cortese","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"2026051402050514000_97.6.479.1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S1474-4422(24)00167-4","article-title":"Neurological disorders caused by novel non-coding repeat expansions: clinical features and differential diagnosis","volume":"23","author":"Vegezzi","year":"2024","journal-title":"Lancet 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