ArticleJournal of medical genetics2012
NOTCH2 mutations in Alagille syndrome.
Article in Journal of medical genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 215 citations in OpenAlex.
- Outcomes of Alagille syndrome following the Kasai operation: a systematic review and meta-analysis.Pediatric surgery international · 2018Pooled it
- A NOTCH2 pathogenic variant alters the osteoblast and vascular cell transcriptome of mouse femurs.Bone · 2026Article
- The Brazilian Alagille syndrome study: New insights from a multicenter national cohort.JPGN reports · 2026Article
- An Overview of Genetics of Moyamoya: BeyondInternational journal of molecular sciences · 2026Review
- Alagille syndrome caused by p.L2014Vfs*10 in NOTCH2: a case report and review of the literature.Journal of medical case reports · 2026Review
- Article
- Hajdu-Cheney Syndrome with Fatal Progressive Basilar Invagination: Illustrative Case.Children (Basel, Switzerland) · 2025Article
- Phenotypic Divergence of JAG1- and NOTCH2-Associated Alagille Syndrome & Disease-Specific NOTCH2 Variant Classification Guidelines.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- A Retrospective Study of Clinical and Genetic Features in a Long-Term Cohort of Mexican Children with Alagille Syndrome.International journal of molecular sciences · 2025Article
- Identifying a novelWorld journal of clinical cases · 2025Article
- The Role of Visual Electrophysiology in Systemic Hereditary Syndromes.International journal of molecular sciences · 2025Review
- Clinical and genetic characteristics of patients with Alagille syndrome in China: identification of six novelTranslational pediatrics · 2024Article
- Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.Progress in retinal and eye research · 2024Review
- Association of Very RareGenes · 2024Article
- Temporal dynamics and stoichiometry in human Notch signaling from Notch synaptic complex formation to nuclear entry of the Notch intracellular domain.Developmental cell · 2024Article
- Diseases of bile duct in children.World journal of gastroenterology · 2024Review
- Aortic Valve Embryology, Mechanobiology, and Second Messenger Pathways: Implications for Clinical Practice.Journal of cardiovascular development and disease · 2024Review
- Diagnosis and management of Alagille and progressive familial intrahepatic cholestasis.Hepatology communications · 2023Article
- Neonatal cholestasis in children with Alpha-1-AT deficiency is a risk for earlier severe liver disease with male predominance.Hepatology communications · 2023Article
- A spatiotemporal Notch interaction map from plasma membrane to nucleus.Science signaling · 2023Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 7 institutions in 5 countries.
Funding
Abstract
backgroundAlagille syndrome (ALGS) is a dominant, multisystem disorder caused by mutations in the Jagged1 (JAG1) ligand in 94% of patients, and in the NOTCH2 receptor in <1%. There are only two NOTCH2 families reported to date. This study hypothesised that additional NOTCH2 mutations would be present in patients with clinical features of ALGS without a JAG1 mutation.
methodsThe study screened a cohort of JAG1-negative individuals with clinical features suggestive or diagnostic of ALGS for NOTCH2 mutations.
resultsEight individuals with novel NOTCH2 mutations (six missense, one splicing, and one non-sense mutation) were identified. Three of these patients met classic criteria for ALGS and five patients only had a subset of features. The mutations were distributed across the extracellular (N=5) and intracellular domains (N=3) of the protein. Functional analysis of four missense, one nonsense, and one splicing mutation demonstrated decreased Notch signalling of these proteins. Subjects with NOTCH2 mutations demonstrated highly variable expressivity of the affected systems, as with JAG1 individuals. Liver involvement was universal in NOTCH2 probands and they had a similar prevalence of ophthalmologic and renal anomalies to JAG1 patients. There was a trend towards less cardiac involvement in the NOTCH2 group (60% vs 100% in JAG1). NOTCH2 (+) probands exhibited a significantly decreased penetrance of vertebral abnormalities (10%) and facial features (20%) when compared to the JAG1 (+) cohort.
conclusionsThis work confirms the importance of NOTCH2 as a second disease gene in ALGS and expands the repertoire of the NOTCH2 related disease phenotype.
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