An unclassified viariant in the fibrillin-1 gene leading to exon skipping in a patient with Marfan syndrome: The use of minigene assay in splicing analysis

Genetic aortic diseases are a group of illnesses characterized by aortic aneurysms or dissection in the presence of an underlying genetic defect. They are part of the broader spectrum of heritable thoracic aortic disease, which also includes those cases of aortic aneurysm or dissection with a positive family history but in whom no genetic cause is identified. Aortic disease in these conditions is a major cause of mortality, justifying clinical and scientific emphasis on the aorta. Aortic valve disease and atrioventricular valve abnormalities are known as important additional manifestations that require careful follow-up and management. The archetype of genetic aortic disease is Marfan syndrome, caused by pathogenic variants in the Fibrillin-1 gene. Given the presence of fibrillin-1 microfibers in the myocardium, myocardial dysfunction and associated arrhythmia are conceivable and have been shown to contribute to morbidity and mortality in patients with Marfan syndrome. In this review, we will discuss data on myocardial disease from human studies as well as insights obtained from the study of mouse models of Marfan syndrome. We will elaborate on the various phenotypic presentations in childhood and in adults and on the topic of arrhythmia. We will also briefly discuss the limited data available on other genetic forms of aortic disease.

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A Case of Neonatal Marfan Syndrome: A Management Conundrum and the Role of a Multidisciplinary Team

Case Reports in Pediatrics ◽

10.1155/2017/8952428 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Elliott J. Carande ◽

Samuel J. Bilton ◽

Satish Adwani

Keyword(s):

Marfan Syndrome ◽

Surgical Intervention ◽

Rare Condition ◽

Mitral Valve Regurgitation ◽

Left Ventricular ◽

Cardiac Complications ◽

Chromosome 15 ◽

Fibrillin 1 ◽

Neonatal Marfan Syndrome

Neonatal Marfan syndrome (nMFS) is a rare condition with a poor prognosis. It is genotypically and phenotypically distinct from the typical Marfan syndrome and carries a poorer prognosis. This case report describes the progression of a 14-month-old girl diagnosed with nMFS at 5 months of age. Her diagnosis followed the identification of a fibrillin-1 mutation (FBN1gene, exon 26, chromosome 15), which is a common locus of nMFS. This patient developed severe cardiac complications resulting in congestive cardiac failure in early life and required major cardiac surgery. Since surgical intervention, our patient is still reliant on a degree of ventilator support, but the patient has gained weight and echocardiography has demonstrated improved left ventricular function and improved tricuspid and mitral valve regurgitation. Therefore, we argue the importance of a cautious multidisciplinary approach to early surgical intervention in cases of nMFS.

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Next generation sequencing as a rapid molecular diagnosis for Marfan syndrome in a Chinese family with mutations in the fibrillin-1 gene

Clinica Chimica Acta ◽

10.1016/j.cca.2014.09.034 ◽

2015 ◽

Vol 439 ◽

pp. 58-60 ◽

Cited By ~ 2

Author(s):

Yan Xiao ◽

Yaxin Liu ◽

Kunqi Yang ◽

Yankun Yang ◽

Xianliang Zhou ◽

...

Keyword(s):

Next Generation Sequencing ◽

Marfan Syndrome ◽

Molecular Diagnosis ◽

Chinese Family ◽

Next Generation ◽

Fibrillin 1 ◽

Generation Sequencing

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Neonatal Marfan syndrome with missense variant of c.3706T>C undergoing bilateral atrioventricular valve replacement

Cardiology in the Young ◽

10.1017/s1047951121003905 ◽

2021 ◽

pp. 1-4

Author(s):

Junpei Kawamura ◽

Kentaro Ueno ◽

Yoshifumi Kawano

Keyword(s):

Marfan Syndrome ◽

Valve Replacement ◽

Tricuspid Valve ◽

Rare Condition ◽

Missense Variant ◽

Tricuspid Valve Replacement ◽

Genetic Syndrome ◽

Fibrillin 1 ◽

Valve Insufficiency ◽

Neonatal Marfan Syndrome

Abstract Neonatal Marfan syndrome is a rare condition with poor prognosis because of severe mitral and/or tricuspid valve insufficiency. Mitral valve replacement is sometimes required in early infancy, while tricuspid valve replacement is rarely done. We report the first infant neonatal Marfan syndrome case with a missense variant of c.3706T>C in the fibrillin-1 gene that was successfully managed by mitral and tricuspid valve replacement. Early multiple-valve replacement may sometimes be required during infant age in this genetic syndrome.

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Genetics of vascular disease: Marfan syndrome and aortic disease

ESC CardioMed ◽

10.1093/med/9780198784906.003.0160 ◽

2018 ◽

pp. 713-715

Author(s):

Dorien Schepers ◽

Bart Loeys

Keyword(s):

Extracellular Matrix ◽

Marfan Syndrome ◽

Transforming Growth Factor Beta ◽

Matrix Protein ◽

Transforming Growth Factor ◽

Aortic Disease ◽

Extracellular Matrix Protein ◽

Genetic Defects ◽

Fibrillin 1 ◽

Growth Factor Beta

Marfan syndrome is an autosomal dominant, multisystemic disorder, presenting with skeletal, ocular, and cardiovascular symptoms. This connective tissue disease is caused by mutations in FBN1, encoding fibrillin-1, which is an important extracellular matrix protein. Marfan syndrome shows significant clinical overlap with Loeys–Dietz syndrome, which is caused by genetic defects in components of the transforming growth factor-beta pathway: TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, and SMAD3. Overlapping clinical features between Marfan syndrome and Loeys–Dietz syndrome include aortic root aneurysm, arachnodactyly, scoliosis, and pectus deformity.

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