Marfan Syndrome: Using genetic maps to lead the way to new diagnostics and treatments

2020 ◽  
Author(s):  
Ines Nannsen
Keyword(s):  
Marfan Syndrome ◽  
Autosomal Dominant ◽  
Genetic Maps ◽  
Diagnostic Tools ◽  
Chromosome 15 ◽  
Connective Tissues ◽  
Dna Mapping ◽  
Heritable Disorder ◽  
Biochemical Level ◽  
Compare And Contrast

Marfan Syndrome is a heritable disorder of connective tissue caused by a mutated extracellular matrix glycoprotein protein, affecting 1 in 5,000 people worldwide. This protein is responsible for support and elasticity meaning that people affected by this disorder manifest with weakened tendons, ligaments and other connective tissues. Patients exhibit a wide variety of symptoms including, scoliosis, abnormally slender digits, vision problems and enlarged blood vessels. Marfan’s follows an autosomal dominant pattern of inheritance and has a penetrance of 100%, meaning that anyone inheriting the gene will be affected by the disease. This study focuses on the developments in the field of DNA mapping and how these advancements have improved the diagnostic tools and treatments for this disease. After exploring the methodology of DNA mapping, the LOD scores for Marfan Syndrome are discussed and compared in order to conclude which chromosome carried the mutation; it was found that chromosome 15 carries. Additionally, the results compare and contrast different genetic markers and identifies a link between markers D15529 and D15545. Although this technology is fairly recent and has thus not been studied as extensively as traditional methods, the information gathered in this research illustrates the methodology of DNA mapping and how; by understanding the gene expression and mutation at a biochemical level, diagnostics and treatments for patients can be tailored specifically to the disease and not just management of the symptoms.

Common Maternal Genetic Syndromes II: Marfan Syndrome

2019 ◽  
Author(s):  
Ali Said Al-Beshri ◽  
Nathaniel H. Robin
Keyword(s):  
Genetic Testing ◽  
Aortic Dissection ◽  
Marfan Syndrome ◽  
Accurate Diagnosis ◽  
Genetic Syndromes ◽  
Connective Tissues ◽  
Ectopia Lentis ◽  
Surgical Interventions ◽  
Obstetric Management ◽  
Careful Physical Examination

Marfan syndrome is an autosomal dominant syndrome that affects various connective tissues including the aorta and skeletal system. It represent a major cause of aortic dissection in individuals with seemingly unremarkable past medical history, and is the most common cause of aortic dissection in pregnancy. Prompt and accurate diagnosis can be lifesaving. Careful physical examination and detailed personal and family history is vital for clinical evaluation. Genetic testing is often needed for accurate diagnosis but result interpretation might be challenging and genetic counseling is always required. Established guidelines can help navigate the challenges in obstetric management, which may include major surgical interventions during or after pregnancy. This review contains 6 figures, 4 tables, and 40 references. Keywords: Marfan syndrome, FBN1, aortic dissection, dilatation, connective tissue, ectopia lentis, pectus, systemic score, Ghent diagnostic criteria, genetic testing.

scholarly journals Marfan Syndrome with Atypical Presentation: A Case Report

2014 ◽  
Vol 4 (2) ◽  
pp. 111-114
Author(s):  
Sharmin Mahbuba ◽  
Fauzia Mohsin ◽  
Rubaiya Islam ◽  
Tahmina Begum
Keyword(s):  
Case Report ◽  
Marfan Syndrome ◽  
Autosomal Dominant ◽  
Connective Tissue Disorder ◽  
Atypical Presentation ◽  
Dominant Trait ◽  
Autosomal Dominant Trait ◽  
Excessive Sweating ◽  
Molecular Cytogenetic ◽  
Molecular Cytogenetic Techniques

Marfan syndrome is an inherited connective tissue disorder that is transmitted as an autosomal dominant trait. These cases can be diagnosed by molecular cytogenetic techniques. A modified Ghent criteria using systemic scoring system can also identify these cases in absence of molecular cytogenetic techniques.We report a case of a 6 year 5 month old boy who presented with the complaints of excessive sweating sinceinfancy and protrusion of both eye balls which was non progressive since early childhood. On examination, some skeletal features of Marfan syndrome was found and echocardiogram showed huge dilatation of root of aorta which helped in diagnosis by scoring system.Birdem Med J 2014; 4(2): 111-114

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

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
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.

Aortic dissection in children and young adults: diagnosis, patients at risk, and outcomes

2003 ◽  
Vol 13 (4) ◽  
pp. 341-344 ◽  
Author(s):  
Eli Zalzstein ◽  
Robert Hamilton ◽  
Nili Zucker ◽  
Samuel Diamant ◽  
Gary Webb
Keyword(s):  
Chest Pain ◽  
Aortic Dissection ◽  
Marfan Syndrome ◽  
Medical Condition ◽  
Young Patients ◽  
Diagnostic Tools ◽  
Cardiac Defects ◽  
Congenital Cardiac Defects ◽  
Ischemic Bowel ◽  
Presenting Symptoms

Objective: To heighten the awareness of pediatricians and pediatric cardiologists to aortic dissection, a potentially dangerous medical condition. Methods: We reviewed the charts of 13 patients, seen in four medical centers, who suffered acute or chronic aortic dissection over the period 1970 through 2000 whilst under the age of 25 years. Results: There were seven male and six female patients, with the mean age at diagnosis being 12.1 years, with a range from one day to 25 years. Congenital cardiac defects were present in five patients, and Marfan syndrome in four. In three of the patients with congenital cardiac defects, aortic dissection developed as a complication of medical procedures. In three patients, dissection followed blunt trauma to the chest. We could not identify any risk factors in one patient. The presenting symptoms included chest pain in four patients, abdominal pain and signs of ischemic bowel in two, non-palpable femoral pulses in one, and obstruction of the superior caval vein in one. Angiography and magnetic resonance imaging were the main diagnostic tools. Overall mortality was 38%. Only six patients had successful surgical outcomes. Conclusion: Due to the rarity of aortic dissection a high index of suspicion is required to reach the diagnosis in a timely manner. It should be considered in young patients complaining of chest pain in association with Marfan syndrome, anomalies of the aortic valve and arch, and chest trauma.

Common Maternal Genetic Syndromes II: Marfan Syndrome

2019 ◽  
Author(s):  
Ali Said Al-Beshri ◽  
Nathaniel H. Robin
Keyword(s):  
Genetic Testing ◽  
Aortic Dissection ◽  
Marfan Syndrome ◽  
Accurate Diagnosis ◽  
Genetic Syndromes ◽  
Connective Tissues ◽  
Ectopia Lentis ◽  
Surgical Interventions ◽  
Obstetric Management ◽  
Careful Physical Examination

Marfan syndrome is an autosomal dominant syndrome that affects various connective tissues including the aorta and skeletal system. It represent a major cause of aortic dissection in individuals with seemingly unremarkable past medical history, and is the most common cause of aortic dissection in pregnancy. Prompt and accurate diagnosis can be lifesaving. Careful physical examination and detailed personal and family history is vital for clinical evaluation. Genetic testing is often needed for accurate diagnosis but result interpretation might be challenging and genetic counseling is always required. Established guidelines can help navigate the challenges in obstetric management, which may include major surgical interventions during or after pregnancy. This review contains 6 figures, 4 tables, and 40 references. Keywords: Marfan syndrome, FBN1, aortic dissection, dilatation, connective tissue, ectopia lentis, pectus, systemic score, Ghent diagnostic criteria, genetic testing.

scholarly journals A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuping Niu ◽  
Sexin Huang ◽  
Zeyu Wang ◽  
Peiwen Xu ◽  
Lijuan Wang ◽  
...  
Keyword(s):  
Real Time ◽  
Marfan Syndrome ◽  
Quantitative Pcr ◽  
Autosomal Dominant ◽  
Clinical Symptoms ◽  
Stop Codon ◽  
Main Pulmonary Artery ◽  
Left Ventricular ◽  
Occurrence Rate ◽  
Chinese Family

Abstract Background Marfan syndrome (MFS) is a common autosomal dominant inherited disease, and the occurrence rate is around 0.1–0.2‰. The causative variant of FNB1 gene accounts for approximately 70–80% of all MFS cases. In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene. This finding extended the variant spectrum of the FBN1 gene and will provide a solution for patients to bear healthy offspring by preimplantation genetic testing or prenatal diagnosis. Case presentation The patient was treated due to tachycardia during excitement in a hospital. Echocardiography showed dilatation of the ascending aorta and main pulmonary artery, mitral regurgitation (mild), tricuspid regurgitation (mild), and abnormal left ventricular filling. Electrocardiograph showed sinus rhythm. In addition, flutters of shadows in front of his eyes and vitreous opacity were present in the patient. Genomic DNA was extracted from peripheral blood samples from members of the family and 100 unrelated controls. Potential variants were screened out by next-generation sequencing and confirmed by MLPA & Sanger sequencing. Real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the relative mRNA quantitation in the patient. A heterozygous nonsense variant c.3217G > T of the FBN1 gene, which resulted in p. Glu1073Term, was identified in both patients. Only wild type bases were found in the cDNA sequence of the patient. Real-time fluorogenic quantitative PCR results showed that the relative expression level of FBN1 cDNA in the patient was only about 21% compared to that of normal individuals. This variant c.3217G > T of the FBN1 gene introduces a Stop codon in the cb-EGF12 domain. We speculated that a premature translational-termination codon (PTC) was located in the mRNA and the target mRNA was disintegrated through a process known as nonsense-mediated mRNA decay (NMD), which led to a significant decrease of the fibrillin-1 protein, eventually causing clinical symptoms in the patient. Conclusions In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene, which eventually led to Marfan syndrome in a Chinese family.

Novel PKD1 Mutations in Patients with Autosomal Dominant Polycystic Kidney Disease

2020 ◽  
Author(s):  
Hyerin Kim ◽  
Hyung-Hoi Kim ◽  
Chulhun L Chang ◽  
Sang Heon Song ◽  
Namhee Kim
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Genetic Diagnosis ◽  
Diagnostic Tools ◽  
Polycystic Kidney ◽  
Prognostic Information ◽  
Panel Test ◽  
Autosomal Dominant Polycystic Kidney ◽  
Clinically Significant

Abstract Objective Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease. Identifying mutated causative genes can provide diagnostic and prognostic information. In this study, we describe the clinical application of a next generation sequencing (NGS)-based, targeted multi-gene panel test for the genetic diagnosis of patients with ADPKD. Methods We applied genetic analysis on 26 unrelated known or suspected patients with ADPKD. A total of 10 genes related to cystic change of kidney were targeted. Detected variants were classified according to standard guidelines. Results We identified 19 variants (detection rate: 73.1%), including PKD1 (n = 18) and PKD2 (n = 1). Of the 18 PKD1 variants, 8 were novel. Conclusion Multigene panel test can be a comprehensive tool in a clinical setting for genetic diagnosis of ADPKD. It allows us to identify clinically significant novel variants and confirm the diagnosis, and these objectives are difficult to achieve using conventional diagnostic tools.

scholarly journals Homozygosity for autosomal dominant Marfan syndrome.

1984 ◽  
Vol 21 (3) ◽  
pp. 173-177 ◽  
Author(s):  
J Chemke ◽  
R Nisani ◽  
A Feigl ◽  
R Garty ◽  
M Cooper ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Autosomal Dominant

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.

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