scholarly journals Is HSPG2 a modifier gene for Marfan syndrome?

2019 ◽  
Author(s):  
Isabela Gerdes Gyuricza ◽  
Rodrigo Barbosa de Souza ◽  
Luis Ernesto Farinha-Arcieri ◽  
Gustavo Ribeiro Fernandes ◽  
Lygia V. Pereira
Keyword(s):  
Connective Tissue ◽  
Mouse Model ◽  
Human Genome ◽  
Marfan Syndrome ◽  
Connective Tissue Disease ◽  
Spinal Column ◽  
Modifier Gene ◽  
Modifier Locus ◽  
Strong Candidate ◽  
Lower Expression

ABSTRACTMarfan syndrome (MFS) is a connective tissue disease caused by mutations in the FBN1 gene. Nevertheless, other genes influence the manifestations of the disease, characterized by high clinical variability even within families. We mapped modifier loci for cardiovascular and skeletal manifestations in the mgΔloxPneo mouse model for MFS and the synthenic loci in the human genome. Corroborating our findings, one of those loci was identified also as a modifier locus in MFS patients. Here we investigate the HSPG2 gene, located in this region, as a candidate modifier gene for MFS. We show a correlation between Fbn1 and Hspg2 expression in spinal column and aorta in non-isogenic mgΔloxPneo mice. Moreover, we show that mice with severe phenotypes present lower expression of Hspg2 than those mildly affected. Thus, we propose that HSPG2 is a strong candidate modifier gene for MFS and its role in modulating disease severity should be investigated in patients.

Manifestações Cardiovasculares em Paciente Portador de Síndrome de Marfan: Relato de Caso / Cardiovascular Manifestations in a Patient With Marfan's Syndrome: Case Report

1970 ◽  
Vol 4 (2) ◽  
pp. 85-95
Author(s):  
Eduardo Tadeu Ramos Almeida ◽  
Fábio Sergio Ferreira Resende Fonseca ◽  
Flávia Sala Pasquinelli
Keyword(s):  
Cardiovascular Disease ◽  
Case Report ◽  
Connective Tissue ◽  
Marfan Syndrome ◽  
Connective Tissue Disease ◽  
Autosomal Dominant ◽  
Patient Survival ◽  
Delayed Diagnosis ◽  
Common Disease ◽  
Dominant Inheritance

Introdução: A síndrome de Marfan (SMF) é uma doença do tecido conjuntivo, com herança autossômica dominante com incidência de 2-3 para cada 10.000 indivíduos.Casuística: Relataremos um caso de um paciente portador de Síndrome de Marfan que foi diagnosticado em nosso serviço, e que evoluiu com as alterações cardiovasculares mais importantes descritos nessa síndrome, foi devidamente tratado e acompanhado. Conhecendo-se a etiologia de caráter hereditário autossômico dominante, investigamos e descrevemos também achados cardiovasculares em outros membros da família do paciente. Discussão: A Síndrome de Marfan pode afetar vários órgãos, incluindo o esqueleto, olhos, coração e vasos sanguíneos, sendo que os dois últimos são os que possuem maior impacto na sobrevida dos pacientes. As manifestações cardiovasculares incluem a doença valvar e o acometimento da aorta. O prolapso da válvula mitral é a anormalidade mais comum, podendo acometer até 100% dos pacientes. A dilatação da raiz da aorta, apesar de menos frequente pode evoluir para dissecção, representando, portanto, a maior causa de morbimortalidade. Conclusão: A Síndrome de Marfan, apesar de ser a doença do tecido conectivo mais comum, possui um diagnóstico difícil devido a manifestações inespecíficas que podem levar a um subdiagnóstico ou um diagnóstico tardio. Palavras-chave Síndrome de Marfan; Doenças do tecido conjuntivo; Doenças cardiovasculares. Introduction: Marfan syndrome (SMF) and a connective tissue disease with autosomal dominant inheritance with an incidence of 2-3 per 10,000 individuals. Case Report: We report a case of a patient with Marfan syndrome who was diagnosed in our service and evolved with the most important cardiovascular changes described in this syndrome, was properly treated and monitored. Knowing the etiology of autosomal dominant hereditary, we also describe and  investigated cardiovascular findings in other members of the patient's family. Discussion: The Marfan Syndrome can affect various organs, including the skeleton, eyes, heart and blood vessels, and the last two are the ones that have the greatest impact on patient survival. Cardiovascular manifestations include valvular disease and involvement of the aorta. The Mitral valve prolapse and the most common abnormality and may affect up to 100% of patients. The dilation of the aortic root, although less frequently can progress to dissection, representing therefore a major cause of morbidity and mortality. Conclusion: The Marfan syndrome, despite being the most common disease of the connective tissue, has a difficult to diagnose due to nonspecific manifestations that can lead to underdiagnosis or delayed diagnosis. Keywords: Marfan syndrome, connective tissue disease, cardiovascular Disease.

Surgery on a dilated aorta associated with a connective tissue disease or inflammatory vasculitis in children and adolescents

2019 ◽  
Vol 29 (5) ◽  
pp. 564-569
Author(s):  
Jae Gun Kwak ◽  
Woong-Han Kim ◽  
Eung Re Kim ◽  
Yoon Jin Kang ◽  
Jooncheol Min ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Connective Tissue ◽  
Children And Adolescents ◽  
Marfan Syndrome ◽  
Connective Tissue Disease ◽  
Medical Records ◽  
Aortic Surgery ◽  
Ascending Aorta ◽  
Functional Class

AbstractIntroduction:This research investigated patients who underwent surgery for a dilated aorta associated with a connective tissue disease or inflammatory vasculitis in children and adolescents.Materials and Methods:The medical records of 11 patients who underwent aortic surgery for dilatation resulting from a connective tissue disease or inflammatory vasculitis between 2000 and 2017 were retrospectively reviewed.Results:The median age and body weight of the patients were 9.6 years (range 5.4 months–15.5 years) and 25.8 kg (range 6.8–81.5), respectively. The associated diseases were Marfan syndrome (n = 3), Loeys-Dietz syndrome (n = 3), Kawasaki disease (n = 1), Takayasu arteritis (n = 1), PHACE syndrome (n = 1), tuberous sclerosis (n = 1), and unknown (n = 1). The most common initially affected area was the ascending aorta. During the 66.4 ± 35.9 months of follow-up, two Marfan syndrome patients died, and four patients (one Marfan syndrome and three Loeys-Dietz syndrome) had repeated aortic operation. Except for one patient, the functional class was well maintained in all patients who were followed up.Conclusion:Cases of surgical treatment for a dilated aorta associated with a connective tissue disease and inflammatory vasculitis are rare in children and adolescents at our institution. Most of the patients in this study showed a tolerable postoperative course. However, the aorta showed progressive dilation over time even after surgical treatment, especially in patients with Loeys-Dietz syndrome. In these patients, close and more frequent regular follow-up is required.

scholarly journals Marfan syndrome; A connective tissue disease at the crossroads of mechanotransduction, TGFβ signaling and cell stemness

2018 ◽  
Vol 71-72 ◽  
pp. 82-89 ◽  
Author(s):  
Francesco Ramirez ◽  
Cristina Caescu ◽  
Elisabeth Wondimu ◽  
Josephine Galatioto
Keyword(s):  
Connective Tissue ◽  
Marfan Syndrome ◽  
Connective Tissue Disease ◽  
Tgfβ Signaling

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.

Banded aggregates containing fibrillin are present in the cartilage matrix adjacent to chondrocytes in individuals affected with scoliosis

1992 ◽  
Vol 50 (1) ◽  
pp. 892-893
Author(s):  
Douglas R. Keene ◽  
Magaret Fairhurst ◽  
Catherine C. Ridgway ◽  
Lynn Y. Sakai
Keyword(s):  
Connective Tissue ◽  
Marfan Syndrome ◽  
Cross Section ◽  
Immunoelectron Microscopy ◽  
Cartilage Matrix ◽  
Negative Stain ◽  
Gene Coding ◽  
Rotary Shadowing

Matrix microfibrils are present in the connective tissue matrices of all tissues. Following standard TEM processing, they appear in cross section as cylindrical fibrils 8-10 nm in diameter, often associated with amorphous elastin. They are also seen in the absence of amorphous elastin, for example in the shallow papillary layer of skin, and also in cartilage matrix (Figure 1). Negative stain and rotary shadowing studies suggest that microfibrils are composed of laterally associated globular structures connected by fine filamentous strands (“ beaded strings”), and that they are extendable. Immunoelectron microscopy has demonstrated that fibrillin, a 350 Kd glycoprotein, is distributed along all microfibrils with a relaxed periodicity of about 54 nm The gene coding for fibrillin has recently been identified and is defective in the Marfan syndrome.

Sign in / Sign up

Export Citation Format

Share Document