NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway
NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway
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DOI：
10.1086/505332
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发表时间：
2006-07-01
影响因子：
9.8
通讯作者：
Spinner, Nancy B.
中科院分区：
文献类型：
--
作者：
McDaniell, Ryan;Warthen, Daniel M.;Spinner, Nancy B.
Alagille综合征（AGS）是由Notch信号通路配体Jagged1（JAG1）基因突变引起的，94%的患者都有这种突变。为了确定没有JAG1突变的患者的病因，我们筛选了11名JAG1突变阴性的先证者，并检测了Notch2受体（NOTCH2）基因的改变。我们发现NOTCH2突变在两个家庭中分离，并确定了五个受影响的个人。肾脏表现，一个小的特点，在AGS，目前在所有受影响的个人。这表明AGS是一种异质性疾病，并涉及人类疾病中的NOTCH 2突变。
Alagille syndrome ( AGS) is caused by mutations in the gene for the Notch signaling pathway ligand Jagged1 ( JAG1), which are found in 94% of patients. To identify the cause of disease in patients without JAG1 mutations, we screened 11 JAG1 mutation-negative probands with AGS for alterations in the gene for the Notch2 receptor ( NOTCH2). We found NOTCH2 mutations segregating in two families and identified five affected individuals. Renal manifestations, a minor feature in AGS, were present in all the affected individuals. This demonstrates that AGS is a heterogeneous disorder and implicates NOTCH2 mutations in human disease.