{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:07:48Z","timestamp":1771002468109,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T00:00:00Z","timestamp":1487289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"University of Szeged"},{"name":"J\u00e1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>Timothy syndrome 1 (TS1) is a rare genetic disorder characterized by multisystem abnormalities including QT prolongation, congenital heart defects, facial dysmorphism, episodic hypoglycemia, and neurological symptoms. A morphological hallmark of TS1 is syndactyly, present in all cases. TS1 is caused by the canonical p.Gly406Arg mutation in the alternatively spliced exon 8A in the <jats:italic>CACNA1C<\/jats:italic> gene, encoding for the main cardiac L\u2010type calcium channel. A variant case of TS1 is reported. The proband had intermittent fetal bradycardia with heart rate of 72\u2009bpm. On the first day of life bradycardia due to 2:1 atrioventricular (AV) block and marked QTc prolongation of 600\u2009ms was noted. On medical therapy with propranolol and mexiletine 1:1 AV conduction returned with QTc prolongation of 470\u2013580\u2009ms. The patient lacked other extracardiac manifestations, most importantly syndactyly, neurological complications or autism. On genetic analysis, the canonical TS1 causing mutation, p.Gly406Arg in exon 8A of the <jats:italic>CACNA1C<\/jats:italic> gene was detected. The <jats:italic>CACNA1C<\/jats:italic> p.Gly406Arg variant was not present in the parents, but was detected in different DNA samples of the index patient. Our case highlight further phenotypic variability in TS. Most importantly, it underlines that the lack of syndactyly does not exclude the presence of a TS1 genotype. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38084","type":"journal-article","created":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T13:51:08Z","timestamp":1487339468000},"page":"784-789","source":"Crossref","is-referenced-by-count":19,"title":["Timothy syndrome 1 genotype without syndactyly and major extracardiac manifestations"],"prefix":"10.1002","volume":"173","author":[{"given":"R\u00f3bert","family":"Sepp","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine and Cardiology Center University of Szeged Szeged Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia","family":"Hategan","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine and Cardiology Center University of Szeged Szeged Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"B\u00e1csi","sequence":"additional","affiliation":[{"name":"Fej\u00e9r County \u201cSzent Gy\u00f6rgy\u201d University Teaching Hospital Sz\u00e9kesfeh\u00e9rv\u00e1r Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judit","family":"Cseklye","sequence":"additional","affiliation":[{"name":"Seqomics Biotechnology Ltd. 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