{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T06:09:58Z","timestamp":1759730998460,"version":"3.41.2"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771366","82001338"],"award-info":[{"award-number":["81771366","82001338"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014764","name":"China International Medical Foundation","doi-asserted-by":"publisher","award":["CIMF-Z-2016-20-1801"],"award-info":[{"award-number":["CIMF-Z-2016-20-1801"]}],"id":[{"id":"10.13039\/501100014764","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of inherited peripheral neuropathies. The wide phenotypic variability may not be completely explained by a single mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims and Methods<\/jats:title><jats:p>To explore the existence of concomitant variants in CMT, we enrolled 189 patients and performed molecular diagnosis by application of next-generation sequencing combined with multiplex ligation-dependent probe amplification. We conducted a retrospective analysis of patients harboring coinherited variants in different genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four families were confirmed to possess variants in two genes, accounting for 2.1% (4\/189) of the total in our cohort. One CMT1 patient with <jats:italic>PMP22<\/jats:italic> duplication and <jats:italic>MPZ<\/jats:italic> variant (c.286A&amp;gt;C, p.K96Q) exhibited moderate neuropathy with infantile onset, while her father possessing <jats:italic>MPZ<\/jats:italic> variant was mildly affected with adolescence onset. A CMT2 patient with heterozygous variants in <jats:italic>MFN2<\/jats:italic> (c.613_622delGTCACCACAG, p.V205Sfs<jats:sup>*<\/jats:sup>26) and <jats:italic>GDAP1<\/jats:italic> (c.713G&amp;gt;T, p.W238L) exhibited childhood onset mild phenotype, while his mother with <jats:italic>MFN2<\/jats:italic> variant developed bilateral <jats:italic>pes cavus<\/jats:italic> only. A CMT2 patient with heterozygous variants in <jats:italic>MFN2<\/jats:italic> (c.839G&amp;gt;A, p.R280H) and <jats:italic>GDAP1<\/jats:italic> (c.3G&amp;gt;T, p.M1?) presented infantile onset and rapid progression, while her father with <jats:italic>MFN2<\/jats:italic> variant presented with absence of deep tendon reflexes. One sporadic CMT2 patient with early onset was confirmed harboring <jats:italic>de novo MFN2<\/jats:italic> variant (c.1835C&amp;gt;T, p.S612F) and heterozygous <jats:italic>GDAP1<\/jats:italic> variant (c.767A&amp;gt;G, p.H256R).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that the possibility of concomitant variants was not uncommon and should be considered when significant intrafamilial clinical heterogeneity is observed.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2021.736704","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T06:25:06Z","timestamp":1643351106000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["One PMP22\/MPZ and Three MFN2\/GDAP1 Concomitant Variants Occurred in a Cohort of 189 Chinese Charcot-Marie-Tooth Families"],"prefix":"10.3389","volume":"12","author":[{"given":"Yongzhi","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunxiang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huadong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binghao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanqian","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengmao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jifeng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beisha","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruxu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/j.1399-0004.1974.tb00638.x","article-title":"Genetic 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