scholarly journals The effect of beta-blockers therapy on progression of thoracic aortic dilatation in the young Marfan syndrome patients: Difference between subtypes of FBN1 gene mutation

2018 ◽  
Vol 10 (3-4) ◽  
pp. 287-288
Author(s):  
Ngoc-Thanh Kim ◽  
Julie Plaisancie ◽  
Thomas Edouard ◽  
Miarisoa Ratsimandresy ◽  
Philippe Acar ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Marfan Syndrome ◽  
Beta Blockers ◽  
Aortic Dilatation ◽  
Fbn1 Gene

Phenotypic Variability in Marfan Syndrome in a Family With a Novel Nonsense FBN1 Gene Mutation

2012 ◽  
Vol 65 (4) ◽  
pp. 380-381 ◽  
Author(s):  
Aránzazu Díaz de Bustamante ◽  
Eva Ruiz-Casares ◽  
M. Teresa Darnaude ◽  
Teresa Perucho ◽  
Gabriel Martínez-Quesada
Keyword(s):  
Gene Mutation ◽  
Marfan Syndrome ◽  
Phenotypic Variability ◽  
Fbn1 Gene

Abstract 11621: Fibrillin-1 Gene Mutations in Left Ventricular Non-Compaction Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
John J Parent ◽  
Jeffrey A Towbin ◽  
John L Jefferies
Keyword(s):  
Extracellular Matrix ◽  
Gene Mutation ◽  
Marfan Syndrome ◽  
Gene Mutations ◽  
Left Ventricular ◽  
Current Evidence ◽  
Causative Gene ◽  
Fbn1 Gene ◽  
Gene Testing ◽  
Fibrillin 1

Introduction: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare and unique cardiomyopathy. Its presentation can range from a benign phenotype to overt heart failure and sudden cardiac death. The genetics of LVNC are not completely understood and current genetic testing has a yield of about 30% in identifying a causative gene mutation. We present a series of patients with LVNC and fibrillin-1 (FBN1) gene mutations. Hypothesis: We hypothesize that FBN1 gene mutations can lead to LVNC by way of its role in the myocardial extracellular matrix during cardiac development. Methods: A retrospective review of all patients with LVNC at our institution was performed for purposes of another investigation. The process unexpectedly identified patients with LVNC and FBN1 gene mutations, as well as LVNC and Marfan syndrome. Results: Approximately 150 patients are followed in our clinic with LVNC. We screened this population and found 51 patients on medical therapy for reduced function. We retrospectively reviewed gene testing in these 51 patients, when available, and identified 5 patients (10%) with an FBN1 gene mutation. All 5 patients had a dilated LVNC phenotype and previous or current evidence of left ventricular dysfunction. Syndrome breakdown as follows: 3 with Marfan, 1 with Shprintzen-Goldberg, and 1 with no identifiable syndrome. Dilated cardiomyopathy/LVNC gene testing was performed in 3 patients; 2 had disease causing myosin heavy chain 7 gene defects and 1 had no defects. Conclusions: The role of FBN1 in the human myocardium is not completely understood but it is expressed in the developing fetal heart and is a component of the myocardial extracellular matrix. Although causation has not been proven by our report, it certainly raises interest in a mechanistic relationship between LVNC and FBN1 given the increased prevalence of Marfan syndrome and probable increased prevalence of FBN1 gene mutations in this cohort of LVNC patients in light of FBN1.

scholarly journals A Recurring FBN1 Gene Mutation in Neonatal Marfan Syndrome

2002 ◽  
Vol 156 (11) ◽  
pp. 1081 ◽  
Author(s):  
Amanda M. Jacobs ◽  
Ivanka Toudjarska ◽  
Andrew Racine ◽  
Petros Tsipouras ◽  
Michael W. Kilpatrick ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Marfan Syndrome ◽  
Fbn1 Gene ◽  
Neonatal Marfan Syndrome

scholarly journals A Novel Heterozygous Intronic Mutation in the FBN1 Gene Contributes to FBN1 RNA Missplicing Events in the Marfan Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Mario Torrado ◽  
Emilia Maneiro ◽  
Juan Pablo Trujillo-Quintero ◽  
Arturo Evangelista ◽  
Alexander T. Mikhailov ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Marfan Syndrome ◽  
Premature Termination Codon ◽  
Connective Tissue Disorder ◽  
Aortic Dilatation ◽  
Functional Protein ◽  
Fbn1 Gene ◽  
Intronic Mutation ◽  
Aortic Pathology ◽  
Fibrillin 1

Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder, mostly caused by mutations in the fibrillin-1 (FBN1) gene. We, by using targeted next-generation sequence analysis, identified a novel intronic FBN1 mutation (the c.2678-15C>A variant) in a MFS patient with aortic dilatation. The computational predictions showed that the heterozygous c.2678-15C>A intronic variant might influence the splicing process by differentially affecting canonical versus cryptic splice site utilization within intron 22 of the FBN1 gene. RT-PCR and Western blot analyses, using FBN1 minigenes transfected into HeLa and COS-7 cells, revealed that the c.2678-15C>A variant disrupts normal splicing of intron 22 leading to aberrant 13-nt intron 22 inclusion, frameshift, and premature termination codon. Collectively, the results strongly suggest that the c.2678-15C>A variant could lead to haploinsufficiency of the FBN1 functional protein and structural connective tissue fragility in MFS complicated by aorta dilation, a finding that further expands on the genetic basis of aortic pathology.

scholarly journals A novel FBN1 gene mutation associated with earlyonset pneumothorax in Marfan syndrome

2016 ◽  
Vol 13 (1) ◽  
pp. 41-45
Author(s):  
Min Ji Park ◽  
Dong Hun Lee ◽  
Young Lim Shin ◽  
Yong Hee Hong
Keyword(s):  
Gene Mutation ◽  
Marfan Syndrome ◽  
Fbn1 Gene

scholarly journals Family history of aortic dissection is not a risk factor in Marfan syndrome with a FBN1 gene mutation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Tchitchinadze ◽  
O Milleron ◽  
L Eliahou ◽  
S Jadoui ◽  
N Ould Ouali ◽  
...  
Keyword(s):  
Risk Factor ◽  
Family History ◽  
Aortic Dissection ◽  
Gene Mutation ◽  
Marfan Syndrome ◽  
Aortic Surgery ◽  
Aortic Disease ◽  
Personal Risk ◽  
Fbn1 Gene ◽  
History Of

Abstract Background A history family of aortic dissection was considered as a risk factor for aortic dissection in patients with Marfan syndrome with a FBN1 mutation. Objectives Evaluate whether a family history of aortic dissection is a risk marker for dissection in this population Methods Retrospective study of patients coming to the reference centre between 1996 and 2018, carrying a FBN1 gene mutation. Pedigrees were obtained for each patient, and familial screening actively pursued. Patients with a family history of aortic dissection were compared with patients without family history of aortic dissection. Results 1700 patients (age 33.2 (±17) years, 51% women) with a FBN1 gene mutation were included. 145 (8,5%) patients underwent aortic dissection at a mean age of 37.9 (±11.4) years and 323 (19%) patients had been operated at 33.8 (±13.9) years. 481 patients had a family history of aortic dissection, including 38 who dissected themselves, and 88 who underwent surgery. 1219 had no family history of aortic dissection, including 107 who dissected themselves, and 235 who underwent surgery. Therefore, the personal risk for aortic dissection was similar in patients with and without a family history of aortic dissection (38/481, i.e. 7.9% vs 107/1219, i.e. 8.8%), as was the personal risk for prophylactic aortic surgery (88/481, i.e. 18.3% vs. 253/1219, i.e. 17.2%), and the risk for either aortic dissection or prophylactic aortic surgery (118/481, i.e. 24.5% vs. 328/1219, i.e. 26.9%). Conclusions In Marfan syndrome with a FBN1 gene mutation, a family history of aortic dissection is not a marker of aortic disease severity. FUNDunding Acknowledgement Type of funding sources: None.

Glutathione system participation in thoracic aneurysms from patients with Marfan syndrome

VASA ◽  
2017 ◽  
Vol 46 (3) ◽  
pp. 177-186 ◽  
Author(s):  
Alejandra María Zúñiga-Muñoz ◽  
Israel Pérez-Torres ◽  
Verónica Guarner-Lans ◽  
Elías Núñez-Garrido ◽  
Rodrigo Velázquez Espejel ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Marfan Syndrome ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Glutathione S Transferase ◽  
Reduced And Oxidized Glutathione ◽  
Total Antioxidant ◽  
Elevated Activity ◽  
Acute Dissection ◽  
Thoracic Aneurysms

Abstract. Background: Aortic dilatation in Marfan syndrome (MFS) is progressive. It is associated with oxidative stress and endothelial dysfunction that contribute to the early acute dissection of the vessel and can result in rupture of the aorta and sudden death. We evaluated the participation of the glutathione (GSH) system, which could be involved in the mechanisms that promote the formation and progression of the aortic aneurysms in MFS patients. Patients and methods: Aortic aneurysm tissue was obtained during chest surgery from eight control subjects and 14 MFS patients. Spectrophotometrical determination of activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO) index, carbonylation, total antioxidant capacity (TAC), and concentration of reduced and oxidized glutathione (GSH and GSSG respectively), was performed in the homogenate from aortic aneurysm tissue. Results: LPO index, carbonylation, TGF-β1, and GR activity were increased in MFS patients (p < 0.04), while TAC, GSH/GSSG ratio, GPx, and GST activity were significantly decreased (p < 0.04). Conclusions: The depletion of GSH, in spite of the elevated activity of GR, not only diminished the activity of GSH-depend GST and GPx, but increased LPO, carbonylation and decreased TAC. These changes could promote the structural and functional alterations in the thoracic aorta of MFS patients.

scholarly journals Unsuspected somatic mosaicism for FBN1 gene contributes to Marfan syndrome

2021 ◽  
Author(s):  
Pauline Arnaud ◽  
Hélène Morel ◽  
Olivier Milleron ◽  
Laurent Gouya ◽  
Christine Francannet ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Somatic Mosaicism ◽  
Variant Calling ◽  
Copy Number Variations ◽  
Pathogenic Variant ◽  
Single Nucleotide Variants ◽  
Bioinformatics Analyses ◽  
Single Nucleotide ◽  
Fbn1 Gene ◽  
Pathogenic Variants

Abstract Purpose Individuals with mosaic pathogenic variants in the FBN1 gene are mainly described in the course of familial screening. In the literature, almost all these mosaic individuals are asymptomatic. In this study, we report the experience of our team on more than 5,000 Marfan syndrome (MFS) probands. Methods Next-generation sequencing (NGS) capture technology allowed us to identify five cases of MFS probands who harbored a mosaic pathogenic variant in the FBN1 gene. Results These five sporadic mosaic probands displayed classical features usually seen in Marfan syndrome. Combined with the results of the literature, these rare findings concerned both single-nucleotide variants and copy-number variations. Conclusion This underestimated finding should not be overlooked in the molecular diagnosis of MFS patients and warrants an adaptation of the parameters used in bioinformatics analyses. The five present cases of symptomatic MFS probands harboring a mosaic FBN1 pathogenic variant reinforce the fact that apparently asymptomatic mosaic parents should have a complete clinical examination and a regular cardiovascular follow-up. We advise that individuals with a typical MFS for whom no single-nucleotide pathogenic variant or exon deletion/duplication was identified should be tested by NGS capture panel with an adapted variant calling analysis.

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