{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:47:05Z","timestamp":1793065625300,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81460199"],"award-info":[{"award-number":["81460199"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160252"],"award-info":[{"award-number":["82160252"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20202BAB206029"],"award-info":[{"award-number":["20202BAB206029"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Distal hereditary motor neuropathy (dHMN) is a heterogeneous group of diseases characterized by exclusive degeneration of peripheral motor nerves, while only 20.0\u201347.8% of dHMN patients are genetically identified. Recently, GGC expansion in the 5\u2019UTR of <jats:italic>NOTCH2NLC<\/jats:italic> has been associated with dHMN. Accordingly, short tandem repeat (STR) should be further explored in genetically unsolved patients with dHMN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 128 patients from 90 unrelated families were clinically diagnosed as dHMN, and underwent a comprehensively genetic screening. Skin biopsies were conducted with routine protocols.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Most patients showed chronic distal weakness of lower limbs (121\/128), while 20 patients initially had asymmetrical involvements, 14 had subclinical sensory abnormalities, 11 had pyramidal impairments, five had cerebellar disturbance, and four had hyperCKmia. The rate of genetic detection was achieved in 36.7% (33\/90), and the rate increased to 46.7% (42\/90) if patients with variants uncertain significance were included. The most common causative genes included chaperone\u2010related genes (8\/33, 24.2%), tRNA synthetase genes (4\/33, 12.1%), and cytoskeleton\u2010related genes (4\/33, 12.1%). Additionally, two dominant inherited families were attributed to abnormal expansion of GGC repeats in the 5\u2018UTR of <jats:italic>NOTCH2NLC<\/jats:italic>; and a patient with dHMN and cerebellar symptoms had CAG repeat expansion in the <jats:italic>ATXN2<\/jats:italic> gene. Skin biopsy from patients with GGC expansion in <jats:italic>NOTCH2NLC<\/jats:italic> revealed typical intranuclear inclusions on histological and ultrastructural examinations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretations<\/jats:title><jats:p>This study further extends the genetic heterogeneity of dHMN. Given some dHMN patients may be associated with nucleotides repeat expansion, STR screening is necessary to perform in genetically unsolved patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51543","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T09:36:37Z","timestamp":1647509797000},"page":"633-643","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genetic spectrum in a cohort of patients with distal hereditary motor neuropathy"],"prefix":"10.1002","volume":"9","author":[{"given":"Chengsi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijie","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"},{"name":"Department of Medical Genetics The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"},{"name":"Department of Medical Genetics The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"},{"name":"Department of Medical Genetics The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing 100034 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1380-3534","authenticated-orcid":false,"given":"Daojun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"},{"name":"Department of Medical Genetics The First Affiliated Hospital of Nanchang University  Nanchang 330006 China"},{"name":"Department of Neurology Peking University People Hospital  Beijing 100044 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2017.03.018"},{"key":"e_1_2_10_3_1","first-page":"1051","volume-title":"Peripheral Neuropathy","author":"Harding AE","year":"1993"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003772"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14734"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0254-5"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14260"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14700"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.603003"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011054"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.733926"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51371"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2006.01166.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(98)00025-X"},{"key":"e_1_2_10_15_1","article-title":"Genetic origin of sporadic cases and RNA toxicity in neuronal intranuclear inclusion disease","author":"Deng J","year":"2021","journal-title":"J Med Genet"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2011.00361.x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1354"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000319696.14225.67"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2012.00442.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0615-4"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50868"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247363"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09196-1"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20602"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.5414\/NP301144"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2016.00081"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.5414\/NP301323"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz218"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15249"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14514"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24024"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26613"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51432"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24612"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51543","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.51543","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51543","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T22:42:14Z","timestamp":1693003334000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,17]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1002\/acn3.51543"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51543","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,17]]},"assertion":[{"value":"2021-12-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}