{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:26:07Z","timestamp":1790475967959,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      Since 2016, biallelic mutations in the membrane metalloendopeptidase (\n                      <jats:italic>MME)<\/jats:italic>\n                      gene have been associated with late\u2010onset recessive CMT2 (CMT2T). More recently, heterozygous mutations have also been identified in familial and sporadic patients with late\u2010onset axonal neuropathy, ranging from subclinical to severe. This indicates that the heterozygous\n                      <jats:italic>MME<\/jats:italic>\n                      variants may not be fully penetrant, or alternatively, that they may be a potential risk factor for neuropathy. Here, we describe the clinical, neurophysiological, and genetic findings of 32 CM2T Italian patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The patients were recruited from four different Italian referral centers. Following a comprehensive battery of neurological, electrophysiological, and laboratory examinations, the patients' DNA was subjected to sequencing in order to identify any variants in the gene. Bioinformatic and modeling analyses were performed to evaluate the identified variants' effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observe a relatively mild axonal sensory\u2010motor neuropathy with a greater impairment of the lower extremities. Biallelic and monoallelic patients exhibit comparable disease severity, with an earlier onset observed in those with biallelic variants. When considering a subgroup with more than 10\u2009years of disease, it becomes evident that biallelic patients exhibit a more severe form of neuropathy. This suggests that they are more prone to quick progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      CM2T has been definitively defined as a late\u2010onset neuropathy, with a typical onset in the fifth to sixth decades of life and a more rapidly progressing worsening for biallelic patients. CMT2T can be included in the neuropathies of the elderly, particularly if\n                      <jats:italic>MME<\/jats:italic>\n                      variants heterozygous patients are included.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jns.12657","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T19:50:01Z","timestamp":1725911401000},"page":"472-486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical and genetic features of\n                    <scp>CMT2T<\/scp>\n                    in\n                    <scp>Italian<\/scp>\n                    patients confirm the importance of\n                    <scp>\n                      <i>MME<\/i>\n                    <\/scp>\n                    pathogenic variants in idiopathic, late\u2010onset axonal neuropathies"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2208-9195","authenticated-orcid":false,"given":"Alessandro","family":"Geroldi","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences Universit\u00e0 di Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"La Barbera","sequence":"additional","affiliation":[{"name":"OU Medical Genetics IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7683-9449","authenticated-orcid":false,"given":"Alessia","family":"Mammi","sequence":"additional","affiliation":[{"name":"OU Medical Genetics IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Origone","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences Universit\u00e0 di Genova  Genoa Italy"},{"name":"OU Medical Genetics IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gaudio","sequence":"additional","affiliation":[{"name":"OU Medical Genetics IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa","family":"Ponti","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences Universit\u00e0 di Genova  Genoa Italy"},{"name":"OU Medical Genetics IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sanguineri","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences Universit\u00e0 di Genova  Genoa Italy"},{"name":"OU Medical Genetics IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Mat\u00e0","sequence":"additional","affiliation":[{"name":"Neurology Unit Azienda Ospedaliero\u2010Universitaria Careggi  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Sperti","sequence":"additional","affiliation":[{"name":"Neurology Unit Azienda Ospedaliero\u2010Universitaria Careggi  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Carboni","sequence":"additional","affiliation":[{"name":"SOD Diagnostica Genetica, Forensic Genetic Unit Azienda Ospedaliero\u2010Universitaria Careggi  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Bellone","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences Universit\u00e0 di Genova  Genoa Italy"},{"name":"OU Medical Genetics IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Gotta","sequence":"additional","affiliation":[{"name":"OU Medical Genetics IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Gemelli","sequence":"additional","affiliation":[{"name":"OU Neurology Clinic IRCCS Ospedale Policlinico San Martino  Genoa 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