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Novel De Novo DLL4 Missense and Highly Accurate Protein Structure Prediction in Adams-Oliver Type 6 Syndrome
Rodrigo Cabrera1,2, Marlon Yesid Barrera Montañez3, Sebastian Ramiro Gil-Quiñones3
1School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT) Universidad del Rosario Bogotá Colombia.
Abstract:
Adams-Oliver syndrome (AOS) is a rare disease classically described with scalp vertex aplasia cutis and terminal transverse limb defects. This syndrome is frequently misdiagnosed by taking each feature of the disease separately. A novel de novo missense variant in DLL4 (c.998G>A, p.Cys333Tyr) was identified by Whole Exome Sequencing (WES), and structural analysis using AlphaFold and PremPS confirmed its pathogenicity by disrupting the NOTCH1 signaling pathway, highlighting the power of AI-driven tools in variant interpretation.
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