{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:10:15Z","timestamp":1787062215105,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T00:00:00Z","timestamp":1499644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS079388"],"award-info":[{"award-number":["R01NS079388"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,1]]},"abstract":"\n Cramp\u2010fasciculation syndrome (\n CFS<\/jats:styled-content>\n ) is a rare muscle hyperexcitability syndrome that presents with muscle cramps, fasciculations, and stiffness, as well as pain, fatigue, anxiety, hyperreflexia, and paresthesias. Although familial cases have been reported, a genetic etiology has not yet been identified. We performed whole\u2010exome sequencing followed by validation and cosegregation analyses on a father\u2010son pair with\n CFS<\/jats:styled-content>\n . Both subjects manifested other hypersensitivity\u2010hyperexcitability symptoms, including asthma, gastroesophageal reflux, migraine, restless legs syndrome, tremor, cold hyperalgesia, and cardiac conduction defects. Most symptoms improved with carbamazepine, consistent with an underlying cation channelopathy. We identified a variant in the transient receptor potential ankyrin\n A1<\/jats:styled-content>\n channel (\n \n TRPA1<\/jats:styled-content>\n <\/jats:italic>\n ) gene that selectively cosegregated with\n CFS<\/jats:styled-content>\n and the other hypersensitivity\u2010hyperexcitability symptoms. This variant (c.\n 2755C<\/jats:styled-content>\n >T) resulted in a premature stop codon at amino acid 919 (p.Arg919*) in the outer pore of the channel.\n TRPA1<\/jats:styled-content>\n is a widely distributed, promiscuous plasmalemmal cation channel that is strongly implicated in the pathophysiology of the specific hypersensitivity\u2010hyperexcitability symptoms observed in these subjects. Thus, we have identified a novel\n \n TRPA1<\/jats:styled-content>\n <\/jats:italic>\n variant that is associated with\n CFS<\/jats:styled-content>\n as part of a generalized hypersensitivity\u2010hyperexcitability disorder. These findings clarify the diverse functional roles of\n TRPA1<\/jats:styled-content>\n , and underscore the importance of this channel as a potential therapeutic target.\n <\/jats:p>","DOI":"10.1111\/cge.13040","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T07:29:49Z","timestamp":1493018989000},"page":"164-168","source":"Crossref","is-referenced-by-count":28,"title":["A novel\n \n TRPA1<\/scp>\n <\/i>\n variant is associated with carbamazepine\u2010responsive cramp\u2010fasciculation syndrome"],"prefix":"10.1111","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3892-6733","authenticated-orcid":false,"given":"M.J.","family":"Nirenberg","sequence":"first","affiliation":[{"name":"Department of Neurology NYU School of Medicine New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Chaouni","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.M.","family":"Biller","sequence":"additional","affiliation":[{"name":"Department of Neurology NYU School of Medicine New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.M.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Department of Neurology NYU School of Medicine New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Pais\u00e1n\u2010Ruiz","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai New York New York"},{"name":"Departments of Psychiatry, Genetics and Genomic Sciences; Mindich Child Health and Development Institute; and Friedman Brain Institute Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,10]]},"reference":[{"issue":"7","key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1212\/WNL.41.7.1021","article-title":"Cramp\u2010fasciculation syndrome: a treatable hyperexcitable peripheral nerve disorder","volume":"41","author":"Tahmoush AJ","year":"1991","journal-title":"Neurology"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-54215-2_23"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-012-1158-z"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.04.030"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00547.2009"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2010.02203.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183811"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010016\u20109908\u20100"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn500083e"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728220802616620"},{"issue":"5","key":"e_1_2_7_12_1","first-page":"535","article-title":"Transient receptor potential channels as novel drug targets in respiratory diseases","volume":"11","author":"Nassini R","year":"2010","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.11.020"},{"issue":"24","key":"e_1_2_7_14_1","first-page":"7111","article-title":"SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy","volume":"24","author":"Bergareche A","year":"2015","journal-title":"Hum Mol Genet"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14367"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00489.2009"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.13040","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T21:59:54Z","timestamp":1696024794000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,10]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1111\/cge.13040"],"URL":"https:\/\/doi.org\/10.1111\/cge.13040","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,10]]}}}