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. 2022 Dec;43(12):1824-1828.
doi: 10.1002/humu.24433. Epub 2022 Jul 16.

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

Jotte Rodrigues Bento  1 , Alice Krebsová  2 , Ilse Van Gucht  1 , Irene Valdivia Callejon  1 , An Van Berendoncks  3 , Pavel Votypka  4 , Ilse Luyckx  1   5 , Petra Peldova  4 , Steven Laga  6 , Marek Havelka  4 , Lut Van Laer  1 , Pavel Trunecka  7 , Nele Boeckx  1 , Aline Verstraeten  1 , Milan Macek  4 , Josephina A N Meester  1 , Bart Loeys  1   5
Affiliations

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

Jotte Rodrigues Bento et al. Hum Mutat. 2022 Dec.

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.

Keywords: Alagille syndrome; JAG1; intracranial aneurysm; thoracic aortic aneurysm.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pedigrees of two families with JAG1 variants. (a) family with p.Cys748Arg variant; (b) family with the c.2114‐5_2119delins18 variant.
Figure 2
Figure 2
Histological staining of elastin (a, d), collagen (b, e), and phosphorylated SMAD2 protein (pSMAD2, brown nuclear staining, c, f) of aortic tissue of a healthy control (top) and patient A:III:11 (bottom). Scale bar: 100 µm.
See this image and copyright information in PMC

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