Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

Oral Everolimus for Treatment of a Giant Left Ventricular Rhabdomyoma in a Neonate—Rapid Tumor Regression Documented by Real Time 3D Echocardiography

The presented case reports on successful treatment with everolimus in a neonate with left ventricular giant rhabdomyoma. The authors used a different dosage regime compared to literature and documented rapid tumor regression by 3D echocardiography.     

83例6个月以下婴儿室间隔缺损的外科治疗

目的 总结外科手术治疗小婴儿期室间隔缺损(VSD)的临床经验.方法 对2000-2005年83例＜6月龄VSD患儿,年龄12 d至6(4.3±1.2)个月,体重3～6.5(5.1±0.8)kg.膜周部VSD 74例,干下型VSD 8例,膜周部并肌部VSD1例.术前中、重度肺动脉高压69例(83.1%).所有患儿均在浅低温体外循环下手术.结果 全组手术死亡4例,手术病死率为4.8%.术后主要并发症为肺动脉高压危象、肺部感染和心律失常.结论 随着麻醉、体外循环、手术技术和围术期监护处理措施的进步,在小婴儿期施行VSD的外科手术已成为安全的治疗方式.术后对肺高压的处理是手术成功的关键.