In vitro experiments showed that the single MPLS mutation p.Glu2759Cysfs*9 appears to perturb proper FBN1 protein aggregation as compared with the classical MFS mutation p.Tyr2596Thrfs*86.
Using Next Generation Sequencing (NGS) followed by Multiplex Ligation-dependent Probe Amplification on NGS-negative samples, we screened FBN1 gene on 124 unrelated patients (101 MFS fulfilling revised Ghent criteria, 20 suspected MFS, 3 MFS-RD) enrolled from 2008 to 2018 at the Multidisciplinary Marfan Clinic, Tor Vergata Hospital, Rome.
In this study, we investigated the correlations between the FBN1 genotype-phenotype and aortic events (aortic dissection and aortic aneurysm) in patients with Marfan syndrome.
In our database, we discovered two families with hitherto unreported co-occurrence of FBN1/FBN2 variants causing phenotypes with mixed or modified MFS/CCA clinical features.
Eleven FBN1 mutations were identified in 12 patients who strictly fulfilled the Ghent criteria for MFS, and 1 FBN1 mutations were detected in 9 patients with suspected MFS by screening the mutations of FBN1.
Our study reports a novel mutation in FBN1 in a Chinese family and to diagnose this family as Marfan syndrome, we also expand the genotype-phenotype correlation of this disease.
The Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue resulting from pathogenic variants of the fibrillin-1 gene (FBN1) with skeletal, cardiac, and ocular involvement.
Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which is modified post-translationally by glycosylation.
The aim of this study was to investigate the effects of sex on bone microarchitecture and mechanical properties in mice with deficient fibrillin-1, a model of human MFS.
<i>FBN1</i> encodes fibrillin 1, a key structural component of the extracellular matrix, and its variants are associated with a wide range of hereditary connective tissues disorders, such as Marfan syndrome (MFS) and mitral valve-aorta-skeleton-skin (MASS) syndrome.
In conclusion, we here identify a 3'UTR mutation of FBN1 in MFS patients, whose molecular mechanism suggest the involvement of the ER stress response in the formation of the aortic aneurysm.
Focus was placed on the aorta, since aortic disease is life threatening in the Marfan syndrome and fibrillin-1 green fluorescence was most abundant in this tissue.
In conclusion, FBN1 variant c.1453C>T, p.(Arg485Cys) is a pathogenic variant that can cause autosomal dominant Marfan syndrome characterized by a high degree of clinical variability and apparently isolated early onset familial abdominal aortic aneurysms.