{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:27:53Z","timestamp":1786512473155,"version":"build-2736575974"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Project of Changsha City","award":["Kq2403012"],"award-info":[{"award-number":["Kq2403012"]}]},{"name":"Postdoctoral Fellowship Program of CPSF","award":["GZC20233175"],"award-info":[{"award-number":["GZC20233175"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M743949"],"award-info":[{"award-number":["2023M743949"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Charcot\u2013Marie\u2013Tooth disease type 2Z (CMT2Z) is an uncommon inherited condition characterized by autosomal dominant inheritance. It is marked by axonal neuropathy, leading to progressive muscle weakness, cramps, and sensory loss.\n                      <jats:italic>MORC2<\/jats:italic>\n                      is one of the candidate pathogenic genes for CMT2Z.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we enrolled two families affected by Charcot\u2013Marie\u2013Tooth (CMT) disease, with both families having probands who exhibit distal lower limb weakness. Whole-exome sequencing (WES) was used to explore the genetic lesion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two heterozygous variants (NM_001303256, c.34G\u202f&amp;gt;\u202fC;p.A12P; NM_001303256, c.848G\u202f&amp;gt;\u202fA;p.R283H) of\n                      <jats:italic>MORC2<\/jats:italic>\n                      gene were found. The c.848G\u202f&amp;gt;\u202fA;p.R283H variant is rare, and the c.34G\u202f&amp;gt;\u202fC;p.A12P variant has not been reported before. Functional studies revealed that the c.848G\u202f&amp;gt;\u202fA;p.R283H variant resulted in reduced transcription of the\n                      <jats:italic>MORC2<\/jats:italic>\n                      gene. The c.34G\u202f&amp;gt;\u202fC;p.A12P variant did not impact\n                      <jats:italic>MORC2<\/jats:italic>\n                      gene transcription, yet it influenced the protein\u2019s half-life and stability. Based on genetic analysis, two probands were subsequently diagnosed with CMT2Z.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our research contributed to the genetic assessment and guidance for these families, reinforcing the notion that\n                      <jats:italic>MORC2<\/jats:italic>\n                      is a potential causative gene for CMT2Z.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1864944","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:39:50Z","timestamp":1786509590000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel MORC2 variants in Charcot\u2013Marie\u2013Tooth disease type 2Z: genetic and functional insights"],"prefix":"10.3389","volume":"13","author":[{"given":"Rong","family":"Tao","sequence":"first","affiliation":[{"name":"Center for Medical Research, Pingshan District Central Hospital of Shenzhen","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ten","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital of Yangzhou University","place":["Yangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangmei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, The School of Life Sciences, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital of Yangzhou University","place":["Yangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, The School of Life Sciences, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital of Yangzhou University","place":["Yangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory Center, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, China"]},{"name":"Laboratory Center, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical 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