McElhinney Doff B, Krantz Ian D, Bason Lynn, Piccoli David A, Emerick Karan M, Spinner Nancy B, Goldmuntz Elizabeth
Division of Cardiology, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pa 19104-4318, USA.
Circulation. 2002 Nov 12;106(20):2567-74. doi: 10.1161/01.cir.0000037221.45902.69.
Cardiovascular anomalies are among the most common features of Alagille syndrome (AGS). Mutations of JAG1 are found in most individuals with AGS. This study was undertaken to determine the spectrum of cardiovascular phenotypes associated with a JAG1 mutation and/or AGS, investigate potential genotype-phenotype correlations, and begin to correlate clinical outcome with genetic pathogenesis.
We reviewed the records of 200 individuals with a JAG1 mutation or AGS. A total of 187 (94%) subjects had evidence of cardiovascular involvement. Cardiovascular anomalies were identified by imaging in 150 subjects (75%), and 37 (19%) had a peripheral pulmonary stenosis murmur with either a normal echocardiogram or no imaging study. Of the 150 subjects with anomalies confirmed by imaging, right-sided anomalies were present in 123 and left-sided anomalies in 22, with both in 12. Seventeen subjects had other anomalies. The most common abnormality was stenosis/hypoplasia of the branch pulmonary arteries (PAs), which was documented by imaging (n=111) or inferred from a peripheral pulmonary stenosis murmur (n=41) in 76% of subjects. Tetralogy of Fallot was present in 23 subjects and was accompanied by pulmonary atresia in 8. Branch PA phenotype differed between individuals with and without a JAG1 mutation. Among subjects with a JAG1 mutation, there was no correlation between the type or location of mutation and the frequency or type of cardiovascular anomaly.
More than 90% of individuals with a JAG1 mutation or AGS have cardiovascular anomalies, with branch PA stenosis the most common abnormality. Cardiovascular phenotype does not correlate with the type or location of JAG1 mutation.
心血管异常是阿拉吉耶综合征（AGS）最常见的特征之一。大多数AGS患者存在JAG1基因突变。本研究旨在确定与JAG1突变和/或AGS相关的心血管表型谱，研究潜在的基因型-表型相关性，并开始将临床结局与遗传发病机制相关联。
我们回顾了200例JAG1突变或AGS患者的记录。共有187例（94%）受试者有心血管受累的证据。150例（75%）受试者通过影像学检查发现心血管异常，37例（19%）受试者在超声心动图正常或未进行影像学检查的情况下有周围肺动脉狭窄杂音。在150例经影像学证实有异常的受试者中，右侧异常123例，左侧异常22例，双侧异常12例。17例受试者有其他异常。最常见的异常是分支肺动脉（PA）狭窄/发育不全，76%的受试者通过影像学记录（n = 111）或从周围肺动脉狭窄杂音推断（n = 41）。23例受试者患有法洛四联症，其中8例伴有肺动脉闭锁。有JAG1突变和无JAG1突变的个体之间分支PA表型不同。在有JAG1突变的受试者中，突变类型或位置与心血管异常的频率或类型之间无相关性。
超过90%的JAG1突变或AGS患者有心血管异常，其中分支PA狭窄是最常见的异常。心血管表型与JAG1突变的类型或位置无关。
