Mutations in KCNQ1, KCNH2, and SCN5A are the major cause of long QT syndrome (LQTS). More than 90% of the genotyped patients have been reported to carry mutations in any of these three genes. Thanks to increasing popularity of next generation sequencer (NGS), novel CACNA1C mutations have been identified among LQTS patients without extra-cardiac phenotypes. We aimed to clarify the frequency of genotypes in LQTS patients in the era of NGS. The study comprised 160 congenital LQTS patients (71 males) registered from November 2015 to September 2018. Inclusion criteria was QTc > 460 ms and Schwartz score ≥ 3. We performed genetic analysis using target gene method by NGS and confirmed the mutations by Sanger method. The median age for genetic screening was 13 (0–68) years. Sixteen patients suffered cardiac arrest, 47 syncope, and 97 were asymptomatic. We identified genetic mutations in 111 (69.4%) patients including 6 CACNA1C (5.4% of the genotyped patients) with 4 asymptomatic patients. Five (3.1%) patients carried double mutations; three out of them with RYR2 and KCNQ1 or KCNH2. In conclusion, CACNA1C screening would be recommended even if the patient is asymptomatic to elucidate the genetic background of the LQTS patients.

KCNQ1，KCNH2和SCN5A中的突变是长QT综合征（LQTS）的主要原因。据报道，超过90％的基因型患者在这三个基因中的任何一个基因上均带有突变。由于下一代音序器（NGS）的日益普及，新颖的CACNA1C已在无心外表型的LQTS患者中鉴定出突变。我们旨在阐明NGS时代LQTS患者的基因型频率。该研究包括2015年11月至2018年9月登记的160例先天性LQTS患者（71名男性）。纳入标准为QTc> 460 ms，Schwartz评分≥3。我们通过NGS使用靶基因方法进行了遗传分析，并通过Sanger方法确认了突变。基因筛查的中位年龄为13（0-68）岁。16例心脏骤停，晕厥47例，无症状97例。我们在111名（69.4％）患者中鉴定出基因突变，其中包括6例CACNA1C（占基因分型患者的5.4％）和4例无症状患者。五名（3.1％）患者进行了双重突变。其中有三个使用RYR2和KCNQ1或KCNH2。总之，即使患者无症状以阐明LQTS患者的遗传背景，也将建议进行CACNA1C筛查。