Disease relevance of Alagille Syndrome

• Serum GH-binding protein levels, measured by a ligand-mediated immunofunctional assay, were significantly higher in children with Alagille syndrome than in children with cirrhosis or GH deficiency [1].
• In the setting of neonatal cholestasis, the findings of microcornea, posterior embryotoxon, mosaic iris stromal hypoplasia, regional peripapillary depigmentation, congenital macular dystrophy, and anomalous optic discs should suggest the diagnosis of Alagille syndrome [2].
• We have recently identified two patients with mutation proven Alagille syndrome who also had unilateral coronal craniosynostosis [3].
• Severe hypodontia and oral xanthomas in Alagille syndrome [4].
• Twelve patients had neonatal hepatitis, 12 biliary atresia, and one each Alagille syndrome and alpha 1-antitrypsin deficiency liver disease [5].

High impact information on Alagille Syndrome

• We demonstrate four distinct coding mutations in JAG1 from four Alagille syndrome families, providing evidence that it is the causal gene for Alagille syndrome [6].
• Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1 [6].
• Mutations in the human Jagged1 gene are responsible for Alagille syndrome [7].
• CONCLUSIONS: The variations of LCAT activity caused by the degree of jaundice in patients with Alagille syndrome are implicated in the abnormal lipid profiles [8].
• Late recurrence of a hepatocellular carcinoma in a patient with incomplete Alagille syndrome [9].

Chemical compound and disease context of Alagille Syndrome

• Cholesterol efflux from Fu5AH cells to the serum of patients with Alagille syndrome. Importance of the hdl-phospholipids/free cholesterol ratio and of the hdl size distribution [10].
• The ratio of cholate to chenodeoxycholate in the younger patients with Alagille syndrome was significantly higher than CBA (P less than 0.001) [11].
• 2-Deoxy-D-glucose uptake and fatty acid content in fibroblast cultures from children with syndromic paucity of interlobular bile ducts (Alagille syndrome) [12].
• Bile acid metabolism in mild arteriohepatic dysplasia [13].
• Use of ursodeoxycholic acid in the treatment of arteriohepatic dysplasia [14].

Biological context of Alagille Syndrome

• Defective intracellular transport and processing of JAG1 missense mutations in Alagille syndrome [15].
• Mice heterozygous for the Jag1 null allele exhibit an eye dysmorphology similar to that of Cm /+ heterozygotes, but do not exhibit other phenotypes characteristic of Cm /+ mice or of humans with Alagille syndrome [16].
• Point mutations in Jagged-1 gene are the cause for Alagille syndrome, associated with paucity of intrahepatic bile ducts [17].
• We report the case of an 8-year-old boy with arteriohepatic dysplasia, in whom high-resolution chromosome study showed a partial deletion of the short arm of chromosome 20, which encompasses subbands p11.23 to p12 [18].
• We report monozygotic twins with Alagille syndrome concordant for a mutation in Jagged1 but discordant for clinical phenotype [19].

Anatomical context of Alagille Syndrome

• BACKGROUND & AIMS: Mutations in Jagged1 , a Notch ligand, cause Alagille syndrome (AGS), a disorder characterized by a paucity of intrahepatic bile ducts (IHBD) [20].
• Human jagged 1 mutants cause liver defect in Alagille syndrome by overexpression of hepatocyte growth factor [21].
• The finding of a conserved form of craniosynostosis in two unrelated patients with Alagille syndrome and mutations in Jagged1 may indicate that Jagged1 plays a role in cranial suture formation [3].
• Hepatocellular carcinoma and obliterated hepatic bile duct were found at postmortem examination in a 4-year-old girl with arteriohepatic dysplasia (Alagille's syndrome) [22].

Gene context of Alagille Syndrome

• ZNF133 was localized to 20p11.2, close to, but probably distinct from, the region deleted in Alagille syndrome [23].
• Mutations in the human JAGGED1 ( JAG1 ) gene, which encodes a ligand for the Notch family of transmembrane receptors, cause the autosomal dominant disorder Alagille syndrome [16].
• SR-BI- and ABCA1-mediated cholesterol efflux to serum from patients with Alagille syndrome [24].
• We have mapped the human Jagged1 gene (JAG1), encoding a ligand for the developmentally important Notch transmembrane receptor, to the Alagille syndrome critical region within 20p12 [6].
• FISH analyses of individuals with 20p12 deletions and affected by Alagille syndrome exclude hES as a candidate gene for this disorder [25].

Analytical, diagnostic and therapeutic context of Alagille Syndrome

• An unusual pattern of Tc-99m IDA scintigraphy was observed in a 20-year-old woman with arteriohepatic dysplasia (Alagille syndrome) [26].
• Alagille syndrome (arteriohepatic dysplasia, AHD) is a well defined genetic disorder with five major features: distinctive facies, cardiovascular anomalies, paucity of interlobular bile ducts (PILBD), ocular anomalies and minor skeletal malformations [27].

References