Kamath B M, Bason L, Piccoli D A, Krantz I D, Spinner N B
Division of Gastroenterology, The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
J Med Genet. 2003 Dec;40(12):891-5. doi: 10.1136/jmg.40.12.891.
Alagille syndrome (AGS) is a multi-system, autosomal dominant disorder with highly variable expressivity, caused by mutations within the Jagged1 (JAG1) gene.
We studied 53 mutation positive relatives of 34 AGS probands to ascertain the frequency of clinical findings in JAG1 mutation carriers.
Eleven of 53 (21%) mutation positive relatives had clinical features that would have led to a diagnosis of AGS. Seventeen of the 53 (32%) relatives had mild features of AGS, revealed only after targeted evaluation following the diagnosis of a proband in their family. Twenty five of the 53 (47%) mutation positive relatives did not meet clinical criteria, and two of these individuals had no features consistent with AGS at all. The frequency of cardiac and liver disease was notably lower in the relatives than in the probands, characterising the milder end of the phenotypic spectrum. The characteristic facies of AGS was the feature with the highest penetrance, occurring almost universally in mutation positive probands and relatives.
This study has implications for genetic counselling of families with AGS and JAG1 mutations.
阿拉吉耶综合征（AGS）是一种多系统常染色体显性疾病，具有高度可变的表达性，由锯齿状蛋白1（JAG1）基因突变引起。
我们研究了34名AGS先证者的53名突变阳性亲属，以确定JAG1突变携带者的临床发现频率。
53名突变阳性亲属中有11名（21%）具有可导致AGS诊断的临床特征。53名亲属中有17名（32%）具有AGS的轻微特征，这些特征仅在其家族中先证者被诊断后进行针对性评估时才被发现。53名突变阳性亲属中有25名（47%）不符合临床标准，其中两名个体完全没有与AGS一致的特征。亲属中心脏病和肝病的发生率明显低于先证者，这是表型谱较轻一端的特征。AGS的特征面容是外显率最高的特征，几乎普遍出现在突变阳性的先证者和亲属中。
本研究对患有AGS和JAG1突变的家庭的遗传咨询具有启示意义。
