Marfan Syndrome Research Today is a free monthly online journal that collates and summarizes the latest research about Marfan Syndrome, including details on genetics, causes, symptoms, treatment.

The Roles of Two Novel FBN1 Gene Mutations in the Genotype-Phenotype Correlations of Marfan Syndrome and Ectopia Lentis Patients with Marfanoid Habitus.

Li D, Yu J, Gu F, Pang X, Ma X, Li R, Liu N, Ma X

Department of Genetics, National Research Institute for Family Planning, Beijing, China., Graduate School of Peking Union Medical College, Beijing, China.

Mutations in the fibrillin-1 (FBN1) gene have been identified in patients with Marfan syndrome (MFS) and Marfan-like connective tissue disorders. In this study, two Chinese families were recruited. The patients in family 1 were well characterized with MFS, while those in family 2 displayed Marfan-like disorders such as ectopia lentis (EL) and marfanoid habitus, but did not develop cardiovascular diseases. We aimed to analyze the pathogenic mutations and their relationships with phenotypes in these two Chinese families. All participants underwent complete physical, ophthalmic, and cardiovascular examinations. The 65 exons and flanking intronic sequences of FBN1 were amplified by polymerase chain reaction, and screened for mutations by denaturing high-performance liquid chromatography and sequencing. One hundred and fifteen unrelated controls were analyzed using the same methods to confirm the mutations. In family 1, we identified the mutation p.C499S in the calcium-binding epidermal growth factor (cbEGF)-like domain 3 of FBN1. In family 2, the mutation p.C908Y was identified in an interdomain region of the hybrid motif 2 linked to the cbEGF-like domain 10. It can be concluded that FBN1 mutations involving cysteine substitutions are usually associated with MFS and EL with some MFS features. Moreover, pathology seemed more serious when the mutations disrupted the three disulfide bridges in the cbEGF-like domains, which was more likely to cause typical MFS than if the mutations occurred in the hybrid motifs. Our data preliminarily establish a genotype-phenotype correlation in the diagnostic process of MFS and predominant EL with Marfan-like features.

Published 12 May 2008 in Genet Test.
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Articles on Marfan Syndrome published 7 May 2008:

Penetration of left and right atrial wall and aortic root by an Amplatzer atrial septal occluder in a nine year old boy with Marfan syndrome: Case report.   J Cardiothorac Surg, 3(1): 25.

ABSTRACT: BACKGROUND: To describe complications associated with Amplatzer septal occluders in a patient with Marfan syndrome CASE PRESENTATION: A nine-year-old boy with Marfan syndrome and a 22 mm atrial septal defect (ASD) was treated successfully by interventional closure of his ASD by placing a 24 mm Amplatzer septal occluder. Follow up examinations showed a good result but an increasing enlargement of aortic root, so the patient was scheduled for operation. Intraoperative findings showed a ... [Abstract] [Full-text]

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Microfibrils are essential elements in elastic and nonelastic tissues contributing to homeostasis and growth factor regulation. Fibrillins form the core of these multicomponent assemblies. Various human genetic disorders, the fibrillinopathies, arise from mutations in fibrillins and are frequently associated with aberrant microfibril assembly. These disorders include Marfan syndrome, Weill-Marchesani syndrome, Beals syndrome, and others. Although homotypic and heterotypic fibrillin ... [Abstract] [Full-text]

Articles on Marfan Syndrome published 1 May 2008:

Determinants of quality of life in marfan syndrome.   Psychosomatics, 49(3): 243-8.

BACKGROUND: Marfan syndrome (MFS) is a rare, heritable disorder that affects connective tissue. Men and women are equally affected. Clinical manifestations involve multiple sites, especially bones and ligaments and heart and blood vessels. OBJECTIVE: Authors sought to investigate quality of life (QoL) in MFS patients, assessing positive and negative sociodemographic factors and self-perceived well-being and functional status. METHOD: Thirty-six patients affected by MFS were interviewed and were ... [Abstract] [Full-text]

Articles on Marfan Syndrome published 25 April 2008:

Long-term doxycycline is more effective than atenolol to prevent thoracic aortic aneurysm in marfan syndrome through the inhibition of matrix metalloproteinase-2 and -9.   Circ Res, 102(8): e73-85.

Beta-blockers, eg, atenolol, are the cornerstone therapy for thoracic aortic aneurysm (TAA) in patients with Marfan syndrome; however, continued aortic dilatation has been reported. We have demonstrated that matrix metalloproteinase (MMP)-2 and -9 were upregulated during progression of TAA in Marfan syndrome, accompanied with degenerated elastic fibers and vasomotor dysfunction. We hypothesized that doxycycline, a nonspecific inhibitor of MMPs, would ameliorate TAA by attenuating elastic fiber ... [Abstract] [Full-text]

FBN1 mutation screening of patients with Marfan syndrome and related disorders: detection of 46 novel FBN1 mutations.   Clin Genet.

Fibrillin-1 gene (FBN1) mutations cause Marfan syndrome (MFS), an inherited connective tissue disorder with autosomal dominant transmission. Major clinical manifestations affect cardiovascular and skeletal apparatuses and ocular and central nervous systems. We analyzed FBN1 gene in 99 patients referred to our Center for Marfan Syndrome and Related Disorders (University of Florence, Florence, Italy): 85 were affected by MFS and 14 by other fibrillinopathies type I. We identified mutations in 80 ... [Abstract] [Full-text]

Articles on Marfan Syndrome published 24 April 2008:

Severe Marfan syndrome due to FBN1 exon deletions.   Am J Med Genet A, 146(10): 1320-1324.

Marfan syndrome is an autosomal dominant condition, with manifestations mainly in the skeletal, ocular, and cardiovascular systems. The disorder is caused by mutations in fibrillin-1 gene (FBN1). The majority of these are family-specific point mutations, with a small number being predicted to cause exon-skipping. To date, there have only been five reports of in-frame exon deletions in FBN1, with the largest of these spanning three exons. Mosaicism is rarely recorded and has only been reported ... [Abstract] [Full-text]

Articles on Marfan Syndrome published 21 April 2008:

Marfan syndrome and sudden death within a family - Aetiologic, molecular and diagnostic issues at autopsy.   J Forensic Leg Med, 15(4): 205-9.

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Articles on Marfan Syndrome published 18 April 2008:

Dilation-dependent activation of platelets and prothrombin in human thoracic ascending aortic aneurysm.   Arterioscler Thromb Vasc Biol, 28(5): 940-6.

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