{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:09:08Z","timestamp":1791342548712,"version":"4.3.1"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,12,13]],"date-time":"2015-12-13T00:00:00Z","timestamp":1449964800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CMTA Charcot-Marie-Tooth Association of the United States"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mitofusin\u20102 (<jats:italic><jats:styled-content style=\"fixed-case\">MFN2<\/jats:styled-content><\/jats:italic>) mutations are the most common cause of autosomal dominant axonal Charcot\u2010Marie\u2010Tooth disease (<jats:styled-content style=\"fixed-case\">CMT<\/jats:styled-content>, type <jats:styled-content style=\"fixed-case\">2A<\/jats:styled-content>), sometimes complicated by additional features such as optic atrophy (<jats:styled-content style=\"fixed-case\">CMT6<\/jats:styled-content>) and upper motor neuron involvement (<jats:styled-content style=\"fixed-case\">CMT5<\/jats:styled-content>). Several pathogenic mutations are reported, mainly acting in a dominant fashion, although few sequence variants behaved as recessive or semidominant in rare homozygous or compound heterozygous patients. We describe a 49\u2010year\u2010old woman with <jats:styled-content style=\"fixed-case\">CMT5<\/jats:styled-content> associated with compound heterozygosity for two <jats:italic><jats:styled-content style=\"fixed-case\">MFN2<\/jats:styled-content><\/jats:italic> variants, one already reported missense mutation (c.<jats:styled-content style=\"fixed-case\">748C<\/jats:styled-content>&gt;T, p.<jats:styled-content style=\"fixed-case\">R250W<\/jats:styled-content>) and a novel nonsense sequence change (c.<jats:styled-content style=\"fixed-case\">1426C<\/jats:styled-content>&gt;T, p.<jats:styled-content style=\"fixed-case\">R476<\/jats:styled-content>*). Her mother, carrying the p.<jats:styled-content style=\"fixed-case\">R250W<\/jats:styled-content> variant, had very late\u2010onset minimal axonal neuropathy, whilst the father harboring the nonsense sequence change had neither clinical nor electrophysiological neuropathy. The missense mutation is likely pathogenic according to <jats:italic>in silico<\/jats:italic> analyses and a previous report, while the nonsense variant is predicted to behave as a null allele. The p.<jats:styled-content style=\"fixed-case\">R250W<\/jats:styled-content> variant behaves as semidominant by causing only a mild, almost subclinical, neuropathy when heterozygous; the nonsense mutation in the father was phenotypically silent, suggesting that haploinsufficiency for <jats:styled-content style=\"fixed-case\">MFN2<\/jats:styled-content> is not disease causative, but was deleterious in the daughter who had only one active mutated <jats:styled-content style=\"fixed-case\">MFN2<\/jats:styled-content> allele.<\/jats:p>","DOI":"10.1111\/jns.12145","type":"journal-article","created":{"date-parts":[[2015,8,26]],"date-time":"2015-08-26T08:25:24Z","timestamp":1440577524000},"page":"380-386","source":"Crossref","is-referenced-by-count":31,"title":["Mutational mechanisms in <i><scp>MFN2<\/scp><\/i>\u2010related neuropathy: compound heterozygosity for recessive and semidominant mutations"],"prefix":"10.1111","volume":"20","author":[{"given":"Giuseppe","family":"Piscosquito","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, Clinic of Central and Peripheral Degenerative Neuropathies Unit IRCCS Foundation, C. Besta Neurological Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Saveri","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Clinic of Central and Peripheral Degenerative Neuropathies Unit IRCCS Foundation, C. Besta Neurological Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Magri","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Applied Technology, Unit of Genetics of Neurodegenerative and Metabolic Disease IRCCS Foundation, C. Besta Neurological Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Ciano","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Applied Technology, Neurophysiopathology and Epilepsy Centre IRCCS Foundation, C. Besta Neurological Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Di Bella","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Applied Technology, Unit of Genetics of Neurodegenerative and Metabolic Disease IRCCS Foundation, C. Besta Neurological Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaela","family":"Milani","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Applied Technology, Unit of Genetics of Neurodegenerative and Metabolic Disease IRCCS Foundation, C. Besta Neurological Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Taroni","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Applied Technology, Unit of Genetics of Neurodegenerative and Metabolic Disease IRCCS Foundation, C. Besta Neurological Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Pareyson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Clinic of Central and Peripheral Degenerative Neuropathies Unit IRCCS Foundation, C. Besta Neurological Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,13]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-009-0188-y"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4798-06.2007"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.629"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.284"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12117"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.05.003"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200211046"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200611080"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821a441e"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6338-11.2012"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2011.00350.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000311275.89032.22"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70158-3"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182242d4d"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000156517.00615.A3"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws049"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31818b6cbc"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl126"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000171345.62270.29"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20797"}],"container-title":["Journal of the Peripheral Nervous System"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjns.12145","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjns.12145","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jns.12145","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T13:41:16Z","timestamp":1696254076000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jns.12145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":20,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1111\/jns.12145"],"URL":"https:\/\/doi.org\/10.1111\/jns.12145","archive":["Portico"],"relation":{},"ISSN":["1085-9489","1529-8027"],"issn-type":[{"value":"1085-9489","type":"print"},{"value":"1529-8027","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12]]}}}