{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:49:46Z","timestamp":1786978186610,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,10,21]],"date-time":"2018-10-21T00:00:00Z","timestamp":1540080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003449","name":"Green Lane Research and Educational Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Isolated cardiac arrhythmia due to a variant in\n                      <jats:italic>CACNA1C<\/jats:italic>\n                      is of recent knowledge. Most reports have been of singleton cases or of quite small families, and estimates of penetrance and expressivity have been difficult to obtain. We here describe a large pedigree, from which such estimates have been calculated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We studied a five\u2010generation family, in which a\n                      <jats:italic>CACNA1C<\/jats:italic>\n                      variant c.2573G&gt;A p.Arg858His co\u2010segregates with syncope and cardiac arrest, documenting electrocardiographic data and cardiac symptomatology. The reported patients\/families from the literature with\n                      <jats:italic>CACNA1C<\/jats:italic>\n                      gene variants were reviewed, and genotype\u2013phenotype correlations are drawn.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The range of phenotype in the studied family is wide, from no apparent effect, through an asymptomatic QT interval prolongation on electrocardiography, to episodes of presyncope and syncope, ventricular fibrillation, and sudden death. QT prolongation showed inconsistent correlation with functional cardiology. Based upon analysis of 28 heterozygous family members, estimates of penetrance and expressivity are derived.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These estimates of penetrance and expressivity, for this specific variant, may be useful in clinical practice. Review of the literature indicates that individual\n                      <jats:italic>CACNA1C<\/jats:italic>\n                      variants have their own particular genotype\u2013phenotype correlations. We suggest that, at least in respect of the particular variant reported here, \u201carrhythmogenic channelopathy\u201d may be a more fitting nomenclature than long QT syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.476","type":"journal-article","created":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T02:10:00Z","timestamp":1540174200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Penetrance and expressivity of the R858H\n                    <i>CACNA1C<\/i>\n                    variant in a five\u2010generation pedigree segregating an arrhythmogenic channelopathy"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2436-2535","authenticated-orcid":false,"given":"R. J. McKinlay","family":"Gardner","sequence":"first","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"Genetic Health Service New Zealand (South Island Hub) Christchurch Hospital  Christchurch New Zealand"},{"name":"Clinical Genetics Group, Department of Women's and Children's Health University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian G.","family":"Crozier","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"Department of Cardiology Christchurch Hospital  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8411-2090","authenticated-orcid":false,"given":"Alex L.","family":"Binfield","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"Department of Paediatrics Christchurch Hospital  Christchurch New Zealand"},{"name":"Department of Paediatrics University of Otago  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4669-8769","authenticated-orcid":false,"given":"Donald R.","family":"Love","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"LabPlus Auckland City Hospital  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4598-4966","authenticated-orcid":false,"given":"Klaus","family":"Lehnert","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"School of Biological Sciences University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1417-1831","authenticated-orcid":false,"given":"Kate","family":"Gibson","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"Genetic Health Service New Zealand (South Island Hub) Christchurch Hospital  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline J.","family":"Lintott","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"Genetic Health Service New Zealand (South Island Hub) Christchurch Hospital  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8166-4014","authenticated-orcid":false,"given":"Russell G.","family":"Snell","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"School of Biological Sciences University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie C.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"School of Biological Sciences University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-1737","authenticated-orcid":false,"given":"Peter P.","family":"Jones","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"Department of Physiology and HeartOtago University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E.","family":"Waddell\u2010Smith","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"Department of Cardiology Auckland City Hospital  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-8526","authenticated-orcid":false,"given":"Martin A.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biomedical Science University of Otago  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3653-0412","authenticated-orcid":false,"given":"Jonathan R.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group  Auckland New Zealand"},{"name":"Department of Cardiology Auckland City Hospital  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,21]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"e0185680","article-title":"Effectiveness of beta\u2010blockers depending on the genotype of congenital long\u2010QT syndrome: A meta\u2010analysis","volume":"12","author":"Ahn J.","year":"2017","journal-title":"Public Library of Science One"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.668392"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00771"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38045"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467208666150518114857"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-014-0446-5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.113.000138"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2014.09.051"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.115.002745"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2010.08.026"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1020"},{"key":"e_1_2_7_13_1","first-page":"e68504","article-title":"Acute myocardial infarction and stress cardiomyopathy following the Christchurch earthquakes","volume":"8","author":"Chan C.","year":"2013","journal-title":"Public Library of Science One"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1180-1"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology7010003"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001635"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37258"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-15-48"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-12-1457"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2013.12.011"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euu063"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34355"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2012.08.005"},{"key":"e_1_2_7_25_1","first-page":"e106982","article-title":"A CACNA1C variant associated with reduced voltage\u2010dependent inactivation, increased CaV1.2 channel window current, and arrhythmogenesis","volume":"9","author":"Hennessey J. A.","year":"2014","journal-title":"Public Library of Science One"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36924"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13019-017-0683-4"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38833"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25827-5"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.06.081"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_7_33_1","first-page":"e0177532","article-title":"A mutation in the CACNA1C gene leads to early repolarization syndrome with incomplete penetrance: A Chinese family study","volume":"12","author":"Liu X.","year":"2017","journal-title":"Public Library of Science One"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-014-1082-4"},{"key":"e_1_2_7_35_1","first-page":"S1885\u20105857(18)3","article-title":"Digenic heterozigosity in SCN5A and CACNA1C explains the variable expressivity of the long QT phenotype in a Spanish family","author":"Nieto\u2010Mar\u00edn P.","year":"2018","journal-title":"Revista Espa\u00f1ola De Cardiologia"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrcr.2018.03.003"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2018.38.1.54"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38084"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502506102"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.09.011"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/chd.12371"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(99)00255-7"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.14797\/mdcj-10-1-29"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euw433"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1159\/000478900"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.01.002"},{"key":"e_1_2_7_47_1","first-page":"7073","article-title":"Genetic analysis of sick sinus syndrome in a family harboring compound CACNA1C and TTN mutations","volume":"17","author":"Zhu Y. B.","year":"2018","journal-title":"Molecular Medicine Reports"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.476","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.476","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T16:48:01Z","timestamp":1694710081000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,21]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1002\/mgg3.476"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.476","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,21]]},"assertion":[{"value":"2018-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00476"}}