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 ANAESTHETIC MANAGEMENT OF A CASE OF MARFAN SYNDROME POSTED FOR BENTALL OPERATION: A CASE REPORT

2020 ◽  
pp. 1-3
Author(s):  
Parasmani Parasmani ◽  
Ankita Yadav ◽  
Mukesh Kumar
Keyword(s):  
Connective Tissue ◽  
Marfan Syndrome ◽  
Heart Valves ◽  
Composite Graft ◽  
Anaesthetic Management ◽  
Connective Tissue Disorder ◽  
Aortic Dilatation ◽  
Autosomal Dominant Trait ◽  
Bentall Operation ◽  
Bentall Procedure

Marfan syndrome is a connective tissue disorder that is inherited as an autosomal dominant trait. [3] These patients have tubular long bones giving ‘Abe Lincon’[3] appearance. Cardio-vasular anomalies are responsible for early deaths in patients of Marfan syndrome. Defective connective tissue in the aorta and heart valves can lead to aortic dilatation, dissection, rupture and prolapse of cardiac valves. [3] Bentall procedure is a type of cardiac surgery involving composite graft replacement of the aortic valve, aortic root and ascending aorta, with the re-implantation of the coronary arteries into the graft.

scholarly journals Clinical relevance of genotype–phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants

2021 ◽  
Author(s):  
Pauline Arnaud ◽  
Olivier Milleron ◽  
Nadine Hanna ◽  
Jacques Ropers ◽  
Nadia Ould Ouali ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Phenotypic Variability ◽  
Premature Termination Codon ◽  
Connective Tissue Disorder ◽  
Vascular Events ◽  
Severe Scoliosis ◽  
Pathogenic Variants ◽  
Fibrillin 1 ◽  
Cysteine Content

Abstract Purpose Marfan syndrome (MFS) is a connective tissue disorder in which several systems are affected with great phenotypic variability. Although known to be associated with pathogenic variants in the FBN1 gene, few genotype–phenotype correlations have been found in proband studies only. Methods In 1,575 consecutive MFS probands and relatives from the most comprehensive database worldwide, we established survival curves and sought genotype–phenotype correlations. Results A risk chart could be established with clinical and genetic data. Premature termination codon variants were not only associated with a shorter life expectancy and a high lifelong risk of aortic event, but also with the highest risk of severe scoliosis and a lower risk for ectopia lentis (EL) surgery. In-frame variants could be subdivided according to their impact on the cysteine content of fibrillin-1 with a global higher severity for cysteine loss variants and the highest frequency of EL surgery for cysteine addition variants. Conclusion This study shows that FBN1 genotype–phenotype correlations exist for both aortic and extra-aortic features. It can be used for optimal risk stratification of patients with a great importance for genetic counseling and personalized medicine. This also provides additional data for the overall understanding of the role of fibrillin-1 in various organs.

Case 68: Unknown Connective Tissue Disorder and Postural Tachycardia Syndrome

2019 ◽  
pp. 353-356
Author(s):  
Peter Novak
Keyword(s):  
Connective Tissue ◽  
Gene Mutation ◽  
Marfan Syndrome ◽  
Connective Tissue Disorder ◽  
Small Fiber Neuropathy ◽  
Postural Tachycardia Syndrome ◽  
Ehlers Danlos Syndrome ◽  
Postural Tachycardia ◽  
Fibrillin 1 ◽  
Danlos Syndrome

The testing showed a typical postural tachycardia syndrome (POTS) pattern but was negative for small fiber neuropathy. Although the patient has marfanoid habitus, she tested negative for the fibrillin-1 gene mutation which underlies the Marfan syndrome; she is more likely for positive for Ehlers-Danlos syndrome.

Cysteine-to-arginine point mutation in a ‘hybrid’ eight-cysteine domain of FBN1: consequences for fibrillin aggregation and microfibril assembly

1995 ◽  
Vol 108 (3) ◽  
pp. 1317-1323 ◽  
Author(s):  
C.M. Kielty ◽  
T. Rantamaki ◽  
A.H. Child ◽  
C.A. Shuttleworth ◽  
L. Peltonen
Keyword(s):  
Connective Tissue ◽  
Point Mutation ◽  
Marfan Syndrome ◽  
Connective Tissue Disease ◽  
Cell Cultures ◽  
Autosomal Dominant ◽  
Gene Encoding ◽  
Fbn1 Gene ◽  
Microfibril Assembly ◽  
Fibrillin 1

Mutations in the FBN1 gene encoding the microfibrillar glycoprotein fibrillin cause Marfan syndrome, a relatively common autosomal dominant connective tissue disease. Causative FBN1 mutations appear to be dispersed throughout the coding frame, and to date no predictable genotype: phenotype correlations have emerged. We have identified a point mutation within an eight-cysteine ‘hybrid’ motif of the fibrillin polypeptide which results in the substitution of an arginine for a cysteine, in a patient severely affected in the cardiovascular, skeletal and ocular systems. We have utilised cell cultures from various tissues of this patient to investigate the effects of this mutation on fibrillin expression and deposition, and the consequences in terms of microfibril assembly and organisation. We have established that there is no difference in the expression of normal and mutant alleles, and fibrillin synthesis, secretion and deposition are also normal. However, the rate of fibrillin aggregation is reduced and microfibrillar assemblies are both remarkably scarce and morphologically abnormal. These data clearly demonstrate that the mutated allele interferes with normal assembly, and strongly implicate this particular region of the fibrillin-1 molecule in stabilising microfibrillar assemblies.

scholarly journals A Case Report of Marfan Syndrome with Literature Review

2015 ◽  
Vol 4 (4) ◽  
pp. 269
Author(s):  
Hemanth Kumar Kalla ◽  
Swarna Kumari ◽  
CH Rama rao ◽  
MKR Parthasarathy ◽  
S Surya prakash Reddy ◽  
...  
Keyword(s):  
Case Report ◽  
Connective Tissue ◽  
Marfan Syndrome ◽  
Clinical Signs ◽  
Connective Tissue Disorder ◽  
Multiple Organ ◽  
Review Of The Literature ◽  
Organ Systems ◽  
Loin Pain ◽  
Routine Physical Examination

Marfan syndrome(MFS) is a connective tissue disorder that affects multiple organ systems. Cardiovascular, ocular, and skeletal abnormalities are cardinal features of the syndrome. Its incidence is among the highest of any heritable disorder.Most patients who have Marfan syndrome are usually diagnosed incidentally when they present for a routine physical examination for various reasons. The purpose of this paper is to provide a review of the literature, as well as describe a 22-year-old male with MFS and right hydroureteronephrosis diagnosed incidentally when he attended our hospital for complaints of fever and right loin pain. This case report emphasizes importance of “Revised Ghent criteria” for the diagnosis of MFS and highlights various clinical signs of MFS<strong>.</strong>

A Case Report of Marfan Syndrome with Literature Review

2015 ◽  
Vol 4 (4) ◽  
pp. 269
Author(s):  
Hemanth Kumar Kalla ◽  
Swarna Kumari ◽  
CH Rama rao ◽  
MKR Parthasarathy ◽  
S Surya prakash Reddy ◽  
...  
Keyword(s):  
Case Report ◽  
Connective Tissue ◽  
Marfan Syndrome ◽  
Clinical Signs ◽  
Connective Tissue Disorder ◽  
Multiple Organ ◽  
Review Of The Literature ◽  
Organ Systems ◽  
Loin Pain ◽  
Routine Physical Examination

Marfan syndrome(MFS) is a connective tissue disorder that affects multiple organ systems. Cardiovascular, ocular, and skeletal abnormalities are cardinal features of the syndrome. Its incidence is among the highest of any heritable disorder.Most patients who have Marfan syndrome are usually diagnosed incidentally when they present for a routine physical examination for various reasons. The purpose of this paper is to provide a review of the literature, as well as describe a 22-year-old male with MFS and right hydroureteronephrosis diagnosed incidentally when he attended our hospital for complaints of fever and right loin pain. This case report emphasizes importance of “Revised Ghent criteria” for the diagnosis of MFS and highlights various clinical signs of MFS<strong>.</strong>

scholarly journals Marfan Syndrome Variability: Investigation of the Roles of Sarcolipin and Calcium as Potential Transregulator of FBN1 Expression

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 421 ◽  
Author(s):  
Louise Benarroch ◽  
Mélodie Aubart ◽  
Marie-Sylvie Gross ◽  
Marie-Paule Jacob ◽  
Pauline Arnaud ◽  
...  
Keyword(s):  
Gene Expression ◽  
Marfan Syndrome ◽  
Messenger Rna ◽  
Calcium Influx ◽  
Surrogate Endpoint ◽  
Connective Tissue Disorder ◽  
Eqtl Analysis ◽  
Chromosome 11 ◽  
Fbn1 Gene ◽  
The Impact

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that displays a great clinical variability. Previous work in our laboratory showed that fibrillin-1 (FBN1) messenger RNA (mRNA) expression is a surrogate endpoint for MFS severity. Therefore, an expression quantitative trait loci (eQTL) analysis was performed to identify trans-acting regulators of FBN1 expression, and a significant signal reached genome-wide significant threshold on chromosome 11. This signal delineated a region comprising one expressed gene, SLN (encoding sarcolipin), and a single pseudogene, SNX7-ps1 (CTD-2651C21.3). We first investigated the region and then looked for association between the genes in the region and FBN1 expression. For the first time, we showed that the SLN gene is weakly expressed in skin fibroblasts. There is no direct correlation between SLN and FBN1 gene expression. We showed that calcium influx modulates FBN1 gene expression. Finally, SLN gene expression is highly correlated to that of the neighboring SNX7-ps1. We were able to confirm the impact of calcium influx on FBN1 gene expression but we could not conclude regarding the role of sarcolipin and/or the eQTL locus in this regulation.

scholarly journals Marfan Syndrome: A Case Report

2012 ◽  
Vol 2012 ◽  
pp. 1-4
Author(s):  
Rajendran Ganesh ◽  
Rajendran Vijayakumar ◽  
Haridoss Selvakumar
Keyword(s):  
Stainless Steel ◽  
Case Report ◽  
Connective Tissue ◽  
Blood Vessel ◽  
Marfan Syndrome ◽  
Autosomal Dominant ◽  
The Body ◽  
Tissue Protein ◽  
Fibrillin 1 ◽  
Systemic Disorder

Marfan syndrome is an autosomal dominant systemic disorder of the connective tissue. Children affected by the Marfan syndrome carry a mutation in one of their two copies of the gene that encodes the connective tissue protein fibrillin-1. Marfan syndrome affects most organs and tissues, especially the skeleton, lungs, eyes, heart, and the large blood vessel that distributes blood from the heart to the rest of the body. A case report of Marfan syndrome has been reported with oral features. The dental problems of the child were treated under general anesthesia and a one-month review showed intact stainless steel crowns' restorations and no signs of secondary caries.

scholarly journals Patient with Marfan Syndrome and a Novel Variant in FBN1 Presenting with Bilateral Popliteal Artery Aneurysm

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Ahmed Mohammad ◽  
Haytham Helmi ◽  
Paldeep S. Atwal
Keyword(s):  
Connective Tissue ◽  
Marfan Syndrome ◽  
Popliteal Artery ◽  
Artery Aneurysm ◽  
Connective Tissue Disorder ◽  
Acute Onset ◽  
The Body ◽  
Leg Pain ◽  
Popliteal Artery Aneurysm ◽  
Ct Angiogram

We present a 43-year-old man with aortic root dilation, mitral valve prolapse, and marfanoid appearance, who presented with acute onset left leg pain. He underwent a Doppler ultrasound that revealed left popliteal artery aneurysm with thrombus. CT angiogram showed bilateral popliteal artery aneurysms. After repairing of his left popliteal artery aneurysm, he was sent for genetic evaluation. He was diagnosed with Marfan syndrome (MFS) based on the revised Ghent criteria and then underwent FBN1 sequencing and deletion/duplication analysis, which detected a novel pathogenic variant in gene FBN1, denoted by c.5872 T>A (p.Cys1958Ser). MFS is a connective tissue disorder with an autosomal dominant inheritance due to pathogenic variants in FBN1 that encodes Fibrillin-1, a major element of the extracellular matrix, and connective tissue throughout the body. MFS involves multiple systems, most commonly the cardiovascular, musculoskeletal, and visual systems. In our case we present a rare finding of bilateral popliteal artery aneurysms in a male patient with MFS.

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