{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T12:37:50Z","timestamp":1740141470076,"version":"3.37.3"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T00:00:00Z","timestamp":1525651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","award":["27\u201014"],"award-info":[{"award-number":["27\u201014"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>Timothy syndrome is characterized by a unique combination of a prolongation of the corrected QT interval of the electrocardiogram and bilateral cutaneous syndactyly of the fingers and the toes and is caused by heterozygous mutations in <jats:italic>CACNA1C<\/jats:italic>, a gene encoding a calcium channel. After the discovery of the <jats:italic>CACNA1C<\/jats:italic> gene as the causative gene for Timothy syndrome, patients with <jats:italic>CACNA1C<\/jats:italic> mutations with QT prolongation but without syndactyly were described. Here, we report a 5\u2010year\u2010old female patient with cutaneous syndactyly, developmental delay, and pulmonary hypertension. Exome analysis showed a previously undescribed <jats:italic>de novo<\/jats:italic> heterozygous mutation in the <jats:italic>CACNA1C<\/jats:italic> gene, p.Arg1024Gly. To our knowledge, this patient is the first to exhibit syndactyly and to carry a <jats:italic>CACNA1C<\/jats:italic> mutation but to not have QT prolongation, which has long been considered an obligatory feature of Timothy syndrome.<\/jats:p>","DOI":"10.1002\/ajmg.a.38833","type":"journal-article","created":{"date-parts":[[2018,5,8]],"date-time":"2018-05-08T06:27:50Z","timestamp":1525760870000},"page":"1657-1661","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Timothy syndrome\u2010like condition with syndactyly but without prolongation of the QT interval"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-6129","authenticated-orcid":false,"given":"Rika","family":"Kosaki","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, National Center for Child Health and Development Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Ono","sequence":"additional","affiliation":[{"name":"Division of Cardiology, National Center for Child Health and Development Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Terashima","sequence":"additional","affiliation":[{"name":"Division of Neulorogy National Center for Child Health and Development Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenjiro","family":"Kosaki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2013.28.5.788"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2014.09.051"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.04.001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37258"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.5152\/AnatolJCardiol.2015.6315"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","unstructured":"Frohler S. Kieslich M. Langnick C. Feldkamp M. Opgen\u2010Rhein B. Berger F. \u2026Chen W.(2014). Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2).1548.","DOI":"10.1186\/1471-2350-15-48"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34355"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36924"},{"issue":"12","key":"e_1_2_7_10_1","first-page":"1123","article-title":"A rare association of long QT syndrome and syndactyly:","volume":"100","author":"Krause U.","year":"2011","journal-title":"Timothy syndrome (LQT 8)."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00944.2011"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.004"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2005.08.024"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9018"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/08998280.2016.11929398"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66903"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.88.2.782"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38084"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502506102"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","unstructured":"Splawski I. Timothy K. W. Sharpe L. M. Decher N. Kumar P. Bloise R. \u2026Keating M. T.(2004). Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.119(1) 19\u201331.","DOI":"10.1016\/j.cell.2004.09.011"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2014.10.015"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","unstructured":"VanDorn C. S. Johnson J. N. Taggart N. W. Thorkelson L. &Ackerman M. J.(2011). QTc values among children and adolescents presenting to the emergency department.128(6) e1395\u20131401.","DOI":"10.1542\/peds.2010-1513"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","unstructured":"Walsh M. A. Turner C. Timothy K. W. Seller N. Hares D. L. James A. F. \u2026McLeod K.(2018). A multicentre study of patients with Timothy syndrome.20(2) 377\u2013385.","DOI":"10.1093\/europace\/euw433"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.38833","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38833","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.38833","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38833","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T04:38:41Z","timestamp":1694407121000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,7]]},"references-count":22,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1002\/ajmg.a.38833"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38833","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2018,5,7]]},"assertion":[{"value":"2017-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}