Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome

Circulation. Genomic and Precision Medicine
Norifumi TakedaIssei Komuro

Abstract

Marfan syndrome can cause life-threatening aortic complications. We investigated the relationship between FBN1 genotype and severe aortopathy (aortic root replacement, type A dissections, and related death). We evaluated 248 patients with pathogenic or likely pathogenic FBN1 variants. The variants were classified as haploinsufficient type (HI, n=93) or dominant-negative type (DN, n=155) based on their location and predicted amino acid alterations, and we examined the effects of the FBN1 genotype on severe aortic events (aortic root replacement, type A dissections, and related death). The cumulative event-free probability was significantly lower in the HI group than in the DN group (adjusted hazard ratio, 2.1; 95% confidence interval, 1.4 -3.2; P<0.001). DN-CD+HI patients should be monitored more carefully than DN-nonCD patients for rapid development of aortic root aneurysms.

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Citations

Jul 25, 2018·International Journal of Molecular Sciences·Norifumi TakedaIssei Komuro
Jun 1, 2018·Circulation. Genomic and Precision Medicine·Julie De BackerLaura Muiño Mosquera
May 24, 2020·Genes·Thomas GrangeGuillaume Jondeau
Aug 10, 2019·Current Opinion in Cardiology·Julie De BackerCathérine Boileau
Jan 22, 2021·Current Cardiology Reports·Stephanie L Harris, Mark E Lindsay
Nov 12, 2020·Clinical Genetics·Amparo HernándizPilar Sepúlveda
Oct 30, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Nazli GharraeeSusan M Lessner

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