Pathogenic variants in JAG1 are known to cause Alagille syndrome (ALGS), a disorder that primarily affects the liver, lung, kidney, and skeleton. Whereas cardiac symptoms are also frequently observed in ALGS, thoracic aortic aneurysms have only been reported sporadically in postmortem autopsies. We here report two families with segregating JAG1 variants that present with isolated aneurysmal disease, as well as the first histological evaluation of aortic aneurysm tissue of a JAG1 variant carrier. Our observations shed more light on the pathomechanisms behind aneurysm formation in JAG1 variant harboring individuals and underline the importance of cardiovascular imaging in the clinical follow-up of such individuals.

Centre of Medical Genetics Antwerp University Hospital University of Antwerp Antwerp Belgium

Department of Biology and Medical Genetics 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Cardiac Surgery Antwerp University Hospital University of Antwerp Antwerp Belgium

Department of Cardiology Antwerp University Hospital University of Antwerp Antwerp Belgium

Department of Cardiology Center for Inherited Cardiovascular Disorders Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Hepatology and Gastroenterology Transplant Center of Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands

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