Isolated aneurysmal disease as an underestimated finding in individuals with JAG1 pathogenic variants.

Steven Laga, Bart Loeys, Josephina A N Meester, Milan Macek, Aline Verstraeten, Nele Boeckx, Pavel Trunecka, Lut Van Laer, Marek Havelka, Jotte Rodrigues Bento, Petra Peldova, Ilse Luyckx, Pavel Votypka, An Van Berendoncks, Irene Valdivia Callejon, Ilse Van Gucht, Alice Krebsová

Journal: Human mutation 2022;43(12):1824-1828

PMID: 35819173

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Abstract

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.

Address: Centre of Medical Genetics, Antwerp University Hospital/University of Antwerp, Antwerp, Belgium.; Department of Cardiology, Center for Inherited Cardiovascular Disorders, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.; Department of Cardiology, Antwerp University Hospital/University of Antwerp, Antwerp, Belgium.; Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Cardiac Surgery, Antwerp University Hospital/University of Antwerp, Antwerp, Belgium.; Department of Hepatology and Gastroenterology, Transplant Center of Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.

DOI: 10.1002/humu.24433

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MeSH Terms: Humans, Jagged-1 Protein, Alagille Syndrome, Heart, Calcium-Binding Proteins