{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T02:30:04Z","timestamp":1776479404405,"version":"3.51.2"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T00:00:00Z","timestamp":1560470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31571294"],"award-info":[{"award-number":["31571294"]}],"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":["31671314"],"award-info":[{"award-number":["31671314"]}],"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":["81771366"],"award-info":[{"award-number":["81771366"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Guangdong Province and Science","award":["2018B030311033"],"award-info":[{"award-number":["2018B030311033"]}]},{"name":"Technology Planning Project of Guangzhou","award":["201707010301"],"award-info":[{"award-number":["201707010301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy exhibiting great clinical and genetic heterogeneity. Here, the identification of two heterozygous missense mutations in the C1orf194 gene at 1p21.2-p13.2 with Charcot-Marie-Tooth disease are reported. Specifically, the p.I122N mutation was the cause of an intermediate form of Charcot-Marie-Tooth disease, and the p.K28I missense mutation predominately led to the demyelinating form. Functional studies demonstrated that the p.K28I variant significantly reduced expression of the protein, but the p.I122N variant increased. In addition, the p.I122N mutant protein exhibited the aggregation in neuroblastoma cell lines and the patient\u2019s peroneal nerve. Either gain-of-function or partial loss-of-function mutations to C1ORF194 can specify different causal mechanisms responsible for Charcot-Marie-Tooth disease with a wide range of clinical severity. Moreover, a knock-in mouse model confirmed that the C1orf194 missense mutation p.I121N led to impairments in motor and neuromuscular functions, and aberrant myelination and axonal phenotypes. The loss of normal C1ORF194 protein altered intracellular Ca2+ homeostasis and upregulated Ca2+ handling regulatory proteins. These findings describe a novel protein with vital functions in peripheral nervous systems and broaden the causes of Charcot-Marie-Tooth disease, which open new avenues for the diagnosis and treatment of related neuropathies.<\/jats:p>","DOI":"10.1093\/brain\/awz151","type":"journal-article","created":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T15:13:59Z","timestamp":1558106039000},"page":"2215-2229","source":"Crossref","is-referenced-by-count":16,"title":["Mutations in C1orf194, encoding a calcium regulator, cause dominant Charcot-Marie-Tooth disease"],"prefix":"10.1093","volume":"142","author":[{"given":"Shun-Chang","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru-Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, P.R. 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