Clinical and molecular genetics of Alagille syndrome
Clinical and molecular genetics of Alagille syndrome
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DOI：
10.1097/00008480-199912000-00015
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发表时间：
1999-12-01
影响因子：
3.6
通讯作者：
Spinner, Nancy B.
中科院分区：
文献类型：
--
作者：
Krantz, Ian D.;Piccoli, David A.;Spinner, Nancy B.
阿拉吉尔综合征 (AGS) 是一种显性遗传性疾病，其特征是胆管缺乏和由此导致的肝脏疾病，并伴有心脏、骨骼、眼部和面部异常。 Jagged1 (JAG1) 已被确定为 AGS 疾病基因。它编码Notch信号通路中参与细胞命运决定的配体。 AGS 是第一个与该途径相关的发育障碍。它表现出高度可变的表达性，如果不进行分子分析，对轻度受影响者的诊断可能会很困难。目前，约 70% 的 AGS 患者检测到 JAG1 突变，包括全部基因缺失以及蛋白质截短、剪接和错义突变。突变位于蛋白质进化保守基序内的整个基因中。整个 JAG1 基因缺失的患者与基因内突变的患者之间没有表型差异。这表明 JAG1 的单倍剂量不足是导致 AGS 的机制。 Curr Opin Pediatr 1999, 11: 558–564© 1999 Lippncott Williams & Wiikins, Inc.
Alagille syndrome (AGS) is a dominanlly inherited disorder characterized by bile duct paucity and resultant liver disease in combination with cardiac, Skeletal, ocular, and facial abnormalities. Jagged1 (JAG1) has been identified as the AGS disease gene. It encodes a ligand in the Notch signaling pathway that is involved in cell fate determination. AGS is the first developmental disorder to be associated with this pathway. It shows highly variable expressivity, and diagnosis in mildly affected persons can be difficult without molecular analysis. Currently, JAG1 mutations are detected in about 70% of patients with AGS and include total gene deletions as well as protein truncating, splicing, and missense mutations. Mutations are located across the gene within the evolutionarily conserved motifs, of the protein. There is no phenotypic difference between patients with deletion of the entire JAG1 gene and those with intragenic mutations. This suggests that haploinsuf-ficiency for JAG1 is a mechanism causing AGS. Curr Opin Pediatr 1999, 11: 558–564© 1999 Lippncott Williams & Wiikins, Inc.