ArticleAmerican journal of human genetics2015
Heterozygous Loss-of-Function Mutations in DLL4 Cause Adams-Oliver Syndrome.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 90 citations in OpenAlex.
- Molecular mechanism study of novel compound heterozygous EOGT mutations leading to Adams-Oliver syndrome type 4.Global medical genetics · 2026Article
- Adams-Oliver Syndrome: A Comprehensive Literature Review of Clinical, Nutritional, Genetic, and Molecular Aspects with Nursing Care Considerations.International journal of molecular sciences · 2025Review
- Mouse scalp development requires Rac1 and SRF for the maintenance of mechanoresponsive mesenchyme.Development (Cambridge, England) · 2025Article
- Adams-Oliver syndrome: an unusual congenital disorder.Oxford medical case reports · 2025Article
- ProteinMolecules (Basel, Switzerland) · 2025Review
- Communication between endothelial cells and osteoblasts in regulation of bone homeostasis: Notch players.Stem cell research & therapy · 2025Review
- UtilizingJournal of developmental biology · 2025Review
- Case Report: A novelFrontiers in pediatrics · 2025Article
- Aplasia Cutis Congenita Pathomechanisms Reveal Key Regulators of Skin and Skin Appendage Morphogenesis.The Journal of investigative dermatology · 2024Review
- BMPR2 Loss Activates AKT by Disrupting DLL4/NOTCH1 and PPARγ Signaling in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2024Article
- Adams-Oliver syndrome: About a case.Clinical case reports · 2024Article
- Disruption of DLL4/NOTCH1 Causes Dysregulated PPARγ/AKT Signaling in Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2024Article
- Adams-Oliver syndrome and associated complications: Report of a family in Colombia and review of the literatureBiomedica : revista del Instituto Nacional de Salud · 2022Article
- The Notch signaling pathway in skeletal muscle health and disease.Muscle & nerve · 2022Review
- Delta-like ligand-4 regulates Notch-mediated maturation of second heart field progenitor-derived pharyngeal arterial endothelial cells.Journal of cellular and molecular medicine · 2022Article
- Notch Signaling in Vascular Endothelial and Mural Cell Communications.Cold Spring Harbor perspectives in medicine · 2022Article
- Notch signalling in healthy and diseased vasculature.Open biology · 2022Review
- Reduced Notch1 Cleavage Promotes the Development of Pulmonary Hypertension.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Isolated aplasia cutis congenita: A report of two cases.Clinical case reports · 2021Article
- Murine Model of Cardiac Defects Observed in Adams-Oliver Syndrome Driven byStem cells and development · 2021Article
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24 authors at 11 institutions in 7 countries.
Funding
Abstract
Adams-Oliver syndrome (AOS) is a rare developmental disorder characterized by the presence of aplasia cutis congenita (ACC) of the scalp vertex and terminal limb-reduction defects. Cardiovascular anomalies are also frequently observed. Mutations in five genes have been identified as a cause for AOS prior to this report. Mutations in EOGT and DOCK6 cause autosomal-recessive AOS, whereas mutations in ARHGAP31, RBPJ, and NOTCH1 lead to autosomal-dominant AOS. Because RBPJ, NOTCH1, and EOGT are involved in NOTCH signaling, we hypothesized that mutations in other genes involved in this pathway might also be implicated in AOS pathogenesis. Using a candidate-gene-based approach, we prioritized DLL4, a critical NOTCH ligand, due to its essential role in vascular development in the context of cardiovascular features in AOS-affected individuals. Targeted resequencing of the DLL4 gene with a custom enrichment panel in 89 independent families resulted in the identification of seven mutations. A defect in DLL4 was also detected in two families via whole-exome or genome sequencing. In total, nine heterozygous mutations in DLL4 were identified, including two nonsense and seven missense variants, the latter encompassing four mutations that replace or create cysteine residues, which are most likely critical for maintaining structural integrity of the protein. Affected individuals with DLL4 mutations present with variable clinical expression with no emerging genotype-phenotype correlations. Our findings demonstrate that DLL4 mutations are an additional cause of autosomal-dominant AOS or isolated ACC and provide further evidence for a key role of NOTCH signaling in the etiology of this disorder.
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