The Genetics and Ocular Findings of Alagille Syndrome

Kim, Ben J.; Fulton, Anne B.

doi:10.1080/08820530701745108

Cited by 59 publications

(31 citation statements)

References 30 publications

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“…42; 98; 150 This disorder is a form of familial intrahepatic cholestasis, with neonatal jaundice and paucity of intrahepatic bile ducts. Many ocular findings have been reported in association with Alagille syndrome, including posterior embryotoxon, pigmentary retinopathy, and optic disc drusen.…”

Section: Association Of Optic Disc Drusen With Other Ocular or Sysmentioning

confidence: 99%

Optic disk drusen in children

Chang

Pineles

2016

Survey of Ophthalmology

112

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Optic disc drusen occur in 0.4% of children and consist of acellular intracellular and extracellular deposits that often become calcified over time. They are typically buried early in life and generally become superficial, and therefore visible, later in childhood, at the average age of 12 years. Their main clinical significance lies in the ability of optic disc drusen, particularly when buried, to simulate true optic disc edema. Misdiagnosing drusen as true disc edema may lead to an invasive and unnecessary workup for elevated intracranial pressure. Ancillary testing, including ultrasonography, fluorescein angiography, fundus autofluorescence, and optical coherence tomography, may aid in the correct diagnosis of optic disc drusen. Complications of optic disc drusen in children include visual field defects, hemorrhages, choroidal neovascular membrane, non-arteritic anterior ischemic optic neuropathy, and retinal vascular occlusions. Treatment options for these complications include ocular hypotensive agents for visual field defects and intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for choroidal neovascular membranes. In most cases, however, children with optic disc drusen can be managed by observation with serial examinations and visual field testing, once true optic disc edema has been excluded.

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Section: Association Of Optic Disc Drusen With Other Ocular or Sysmentioning

confidence: 99%

Optic disk drusen in children

Chang

Pineles

2016

Survey of Ophthalmology

112

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“…This malady is associated with the mutations in the nuclear receptor DAX1 [120]. Alagille syndrome affects the liver, heart, and other systems of the body and is caused by mutations in the JAG1 gene encoding a ligand for the Notch receptor and therefore playing a crucial role in a critical signaling pathway during development [121].…”

Section: Multi-class Diseasesmentioning

confidence: 99%

Unfoldomics of Human Genetic Diseases: Illustrative Examples of Ordered and Intrinsically Disordered Members of the Human Diseasome

Midic

Oldfield

Dunker³

et al. 2009

PPL

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“…The hepatic cell fate decision is thought to be largely dependent on Notch signaling (39)(40)(41)(42)(43)(44). We therefore examined the expression of Notch, a target of Fbxw7, in the Fbxw7-deficient liver.…”

Section: Conditional Inactivation Of Fbxw7 In the Liver By 2 Cre-loxpmentioning

confidence: 99%

Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver

et al. 2011

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E3 ubiquitin ligase complexes of the SCF type consist of ring-box 1 (Rbx1), cullin 1 (Cul1), S-phase kinase-associated protein 1 (Skp1), and a member of the F-box family of proteins. The identity of the F-box protein determines the substrate specificity of the complex. The F-box family member F-box-and WD repeat domain-containing 7 (Fbxw7; also known as Fbw7, SEL-10, hCdc4, and hAgo) targets for degradation proteins with wide-ranging functions, and uncovering its in vivo role has been difficult, because Fbxw7 -/-embryos die in utero. Using two different Cre-loxP systems (Mx1-Cre and Alb-Cre), we generated mice with liver-specific null mutations of Fbxw7. Hepatic ablation of Fbxw7 resulted in hepatomegaly and steatohepatitis, with massive deposition of triglyceride, a phenotype similar to that observed in humans with nonalcoholic steatohepatitis. Both cell proliferation and the abundance of Fbxw7 substrates were increased in the Fbxw7-deficient liver. Long-term Fbxw7 deficiency resulted in marked proliferation of the biliary system and the development of hamartomas. Fbxw7 deficiency also skewed the differentiation of liver stem cells toward the cholangiocyte lineage rather than the hepatocyte lineage in vitro. This bias was corrected by additional loss of the Notch cofactor RBP-J, suggesting that Notch accumulation triggered the abnormal proliferation of the biliary system. Together, our results suggest that Fbxw7 plays key roles, regulating lipogenesis and cell proliferation and differentiation in the liver.

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The Genetics and Ocular Findings of Alagille Syndrome

Cited by 59 publications

References 30 publications

Optic disk drusen in children

Optic disk drusen in children

Unfoldomics of Human Genetic Diseases: Illustrative Examples of Ordered and Intrinsically Disordered Members of the Human Diseasome

Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver

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