{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:15:03Z","timestamp":1787015703207,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,4,10]],"date-time":"2022-04-10T00:00:00Z","timestamp":1649548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021566","name":"Fundaci\u00f3n Isabel Gemio","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021566","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["PROMETEO\/2018\/13"],"award-info":[{"award-number":["PROMETEO\/2018\/13"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01178"],"award-info":[{"award-number":["PI19\/01178"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01374"],"award-info":[{"award-number":["PI18\/01374"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/00403"],"award-info":[{"award-number":["PI16\/00403"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We aim to present data obtained from three patients belonging to three unrelated families with an infantile onset demyelinating neuropathy associated to somatic and neurodevelopmental delay and to describe the underlying genetic changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed whole\u2010exome sequencing on genomic DNA from the patients and their parents and reviewed the clinical, muscle and nerve data, the serial neurophysiological studies, brain and muscle MRIs, as well as the respiratory chain complex activity in the muscle of the three index patients. Computer modelling was used to characterise the new missense variant detected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All three patients had a short stature, delayed motor milestone acquisition, intellectual disability and cerebellar abnormalities associated with a severe demyelinating neuropathy, with distinct morphological features. Despite the proliferation of giant mitochondria, the mitochondrial respiratory chain complex activity in skeletal muscle was normal, except in one patient in whom there was a mild decrease in complex I enzyme activity. All three patients carried the same two compound heterozygous variants of the\n                      <jats:italic>TRMT5<\/jats:italic>\n                      (tRNA Methyltransferase 5) gene, one known pathogenic frameshift mutation [c.312_315del (p.Ile105Serfs*4)] and a second rare missense change [c.665\u2009T\u2009&gt;\u2009C (p.Ile222Thr)]. TRMT5 is a nuclear\u2010encoded protein involved in the post\u2010transcriptional maturation of mitochondrial tRNA. Computer modelling of the human TRMT5 protein structure suggests that the rare p.Ile222Thr mutation could affect the stability of tRNA binding.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study expands the phenotype of mitochondrial disorders caused by\n                      <jats:italic>TRTM5<\/jats:italic>\n                      mutations and defines a new form of recessive demyelinating peripheral neuropathy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12817","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:33:16Z","timestamp":1648427596000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A novel\n                    <i>TRMT5<\/i>\n                    mutation causes a complex inherited neuropathy syndrome: The role of nerve pathology in defining a demyelinating neuropathy"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8537-1318","authenticated-orcid":false,"given":"Herminia","family":"Argente\u2010Escrig","sequence":"first","affiliation":[{"name":"Neuromuscular and Ataxias Research Group Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia Spain"},{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Rare Diseases Joint Unit IIS La Fe \u2013 CIPF  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0532-2872","authenticated-orcid":false,"given":"Juan J.","family":"V\u00edlchez","sequence":"additional","affiliation":[{"name":"Neuromuscular and Ataxias Research Group Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia Spain"},{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Rare Diseases Joint Unit IIS La Fe \u2013 CIPF  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7206-5362","authenticated-orcid":false,"given":"Marina","family":"Frasquet","sequence":"additional","affiliation":[{"name":"Neuromuscular and Ataxias Research Group Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia Spain"},{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Rare Diseases Joint Unit IIS La Fe \u2013 CIPF  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2349-7481","authenticated-orcid":false,"given":"Nuria","family":"Muelas","sequence":"additional","affiliation":[{"name":"Neuromuscular and Ataxias Research Group Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia Spain"},{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Rare Diseases Joint Unit IIS La Fe \u2013 CIPF  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Azor\u00edn","sequence":"additional","affiliation":[{"name":"Neuromuscular and Ataxias Research Group Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia Spain"},{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Rare Diseases Joint Unit IIS La Fe \u2013 CIPF  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"V\u00edlchez","sequence":"additional","affiliation":[{"name":"Neuromuscular and Ataxias Research Group Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia Spain"},{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"},{"name":"Rare Diseases Joint Unit IIS La Fe \u2013 CIPF  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Millet\u2010Sancho","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Department of Clinical Neurophysiology Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Pitarch","sequence":"additional","affiliation":[{"name":"Neuropediatrics Unit, Department of Pediatrics Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Tom\u00e1s\u2010Vila","sequence":"additional","affiliation":[{"name":"Neuropediatrics Unit, Department of Pediatrics Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3043-7938","authenticated-orcid":false,"given":"Juan F.","family":"V\u00e1zquez\u2010Costa","sequence":"additional","affiliation":[{"name":"Neuromuscular and Ataxias Research Group Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia Spain"},{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Rare Diseases Joint Unit IIS La Fe \u2013 CIPF  Valencia Spain"},{"name":"Department of Medicine Universitat de V\u00e0lencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Mas\u2010Estell\u00e9s","sequence":"additional","affiliation":[{"name":"Neurorradiology Section\u2010ASCIRES, Radiology Department. Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Marco\u2010Mar\u00edn","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Instituto de Biomedicina de Valencia (IBV\u2010CSIC)  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4435-1809","authenticated-orcid":false,"given":"Carmen","family":"Espin\u00f3s","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Rare Diseases Joint Unit IIS La Fe \u2013 CIPF  Valencia Spain"},{"name":"Unit of Rare Neurodegenerative Diseases Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF)  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Serrano\u2010Lorenzo","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Mitochondrial and Neuromuscular Disorders Research Group Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Martin","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Mitochondrial and Neuromuscular Disorders Research Group Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3774-9854","authenticated-orcid":false,"given":"Vincenzo","family":"Lupo","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Rare Diseases Joint Unit IIS La Fe \u2013 CIPF  Valencia Spain"},{"name":"Unit of Rare Neurodegenerative Diseases Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF)  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4716-2667","authenticated-orcid":false,"given":"Teresa","family":"Sevilla","sequence":"additional","affiliation":[{"name":"Neuromuscular and Ataxias Research Group Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia Spain"},{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER)  Valencia Spain"},{"name":"Rare Diseases Joint Unit IIS La Fe \u2013 CIPF  Valencia Spain"},{"name":"Department of Medicine Universitat de V\u00e0lencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000735"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u2010444\u201052902\u20102.00049\u20107"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102016\u2010313960"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01799116"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.126"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00079"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi049671q"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.06.011"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004657"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11080855"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2019.03.002"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2009.05.001"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg202"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114135"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2009.09.005"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2016.07.014"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.04.001"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20108\u201096"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a4a518"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102015\u2010103500"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.149"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx138"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25854"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12467"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1653"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.22019"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12817","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.12817","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:51Z","timestamp":1692835251000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,10]]},"references-count":26,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1111\/nan.12817"],"URL":"https:\/\/doi.org\/10.1111\/nan.12817","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,10]]},"assertion":[{"value":"2022-01-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12817"}}