27 results on '"Arbustini, Eloisa"'
Search Results
2. Mitochondrial cardiomyopathies: how to identify candidate pathogenic mutations by mitochondrial DNA sequencing, MITOMASTER and phylogeny
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Zaragoza, Michael V, Brandon, Martin C, Diegoli, Marta, Arbustini, Eloisa, and Wallace, Douglas C
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Cardiovascular ,Human Genome ,Heart Disease ,Genetics ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Adolescent ,Adult ,Cardiomyopathies ,Child ,DNA ,Mitochondrial ,Databases ,Genetic ,Echocardiography ,Female ,Genes ,Mitochondrial ,Genetic Variation ,Humans ,Infant ,Italy ,Male ,Middle Aged ,Mitochondria ,Mitochondrial Diseases ,Mutation ,Pedigree ,Phylogeny ,Sequence Analysis ,DNA ,mitochondria ,cardiomyopathies ,genetic variation ,phylogeny ,genetic databases ,Clinical Sciences ,Genetics & Heredity - Abstract
Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. Owing to a high mutation rate, mtDNA defects may occur at any nucleotide in its 16 569 bp sequence. Complete mtDNA sequencing may detect pathogenic mutations, which can be difficult to interpret because of normal ethnic/geographic-associated haplogroup variation. Our goal is to show how to identify candidate mtDNA mutations by sorting out polymorphisms using readily available online tools. The purpose of this approach is to help investigators in prioritizing mtDNA variants for functional analysis to establish pathogenicity. We analyzed complete mtDNA sequences from 29 Italian patients with mitochondrial cardiomyopathy or suspected disease. Using MITOMASTER and PhyloTree, we characterized 593 substitution variants by haplogroup and allele frequencies to identify all novel, non-haplogroup-associated variants. MITOMASTER permitted determination of each variant's location, amino acid change and evolutionary conservation. We found that 98% of variants were common or rare, haplogroup-associated variants, and thus unlikely to be primary cause in 80% of cases. Six variants were novel, non-haplogroup variants and thus possible contributors to disease etiology. Two with the greatest pathogenic potential were heteroplasmic, nonsynonymous variants: m.15132T>C in MT-CYB for a patient with hypertrophic dilated cardiomyopathy and m.6570G>T in MT-CO1 for a patient with myopathy. In summary, we have used our automated information system, MITOMASTER, to make a preliminary distinction between normal mtDNA variation and pathogenic mutations in patient samples; this fast and easy approach allowed us to select the variants for traditional analysis to establish pathogenicity.
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- 2011
3. European reference network for rare vascular diseases (VASCERN) consensus statement for the screening and management of patients with pathogenic ACTA2 variants
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van de Laar, Ingrid M. B. H., Arbustini, Eloisa, Loeys, Bart, Björck, Erik, Murphy, Lise, Groenink, Maarten, Kempers, Marlies, Timmermans, Janneke, Roos-Hesselink, Jolien, Benke, Kalman, Pepe, Guglielmina, Mulder, Barbara, Szabolcs, Zoltan, Teixidó-Turà, Gisela, Robert, Leema, Emmanuel, Yaso, Evangelista, Arturo, Pini, Alessandro, von Kodolitsch, Yskert, Jondeau, Guillaume, and De Backer, Julie
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- 2019
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4. 2023 ESC Guidelines for the management of cardiomyopathies: Developed by the task force on the management of cardiomyopathies of the European Society of Cardiology (ESC).
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Arbelo, Elena, Protonotarios, Alexandros, Gimeno, Juan R, Arbustini, Eloisa, Barriales-Villa, Roberto, Basso, Cristina, Bezzina, Connie R, Biagini, Elena, Blom, Nico A, Boer, Rudolf A de, Winter, Tim De, Elliott, Perry M, Flather, Marcus, Garcia-Pavia, Pablo, Haugaa, Kristina H, Ingles, Jodie, Jurcut, Ruxandra Oana, Klaassen, Sabine, Limongelli, Giuseppe, and Loeys, Bart
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VENTRICULAR outflow obstruction ,MELAS syndrome ,CARDIOMYOPATHIES ,TAKOTSUBO cardiomyopathy ,ARRHYTHMOGENIC right ventricular dysplasia ,SARS-CoV-2 ,TASK forces - Abstract
The aim is to provide healthcare professionals with a practical diagnostic and treatment framework for patients of all ages and, as an increasing number of patients have a known genetic basis for their disease, the guideline also considers the implications of a diagnosis for families and provides advice on reproduction and contraception. Keywords: Guidelines; Arrhythmia; Arrhythmogenic right ventricular cardiomyopathy; Cardiomyopathies; Diagnosis; Dilated cardiomyopathy; Genetics; Genetic counselling; Genetic testing; Hypertrophic cardiomyopathy; Implantable cardioverter defibrillator; Management; Multimodality imaging; Non-dilated left ventricular cardiomyopathy; Pregnancy; Restrictive cardiomyopathy; Risk stratification; Screening; Sports; Sudden cardiac death EN Guidelines Arrhythmia Arrhythmogenic right ventricular cardiomyopathy Cardiomyopathies Diagnosis Dilated cardiomyopathy Genetics Genetic counselling Genetic testing Hypertrophic cardiomyopathy Implantable cardioverter defibrillator Management Multimodality imaging Non-dilated left ventricular cardiomyopathy Pregnancy Restrictive cardiomyopathy Risk stratification Screening Sports Sudden cardiac death 3503 3626 124 10/04/23 20231001 NES 231001 Table of contents 1. ESC Guidelines do not override the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient or the patient's caregiver where appropriate and/or necessary. The NDLVC phenotype will include individuals that up until now may have variably been described as having DCM (but without LV dilatation), arrhythmogenic left ventricular cardiomyopathy (ALVC), left-dominant ARVC, or arrhythmogenic DCM (but often without fulfilling diagnostic criteria for ARVC) ( I Figure 3 i ). [Extracted from the article]
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- 2023
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5. When Genes, More Than Phenotype, Identify Different Diseases: The Case of Nonsyndromic HTAA/D.
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Arbustini, Eloisa, Giuliani, Lorenzo, and Di Toro, Alessandro
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GENETICS , *AORTIC valve , *PATHOGENIC microorganisms , *ECHOCARDIOGRAPHY , *CONNECTIVE tissues , *PHENOTYPES , *THORACIC aneurysms , *DISSECTING aneurysms - Published
- 2018
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6. Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial Function of the European Society of Cardiology.
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Bondue, Antoine, Arbustini, Eloisa, Bianco, Anna, Ciccarelli, Michele, Dawson, Dana, Rosa, Matteo De, Hamdani, Nazha, Hilfiker-Kleiner, Denise, Meder, Benjamin, and Leite-Moreira, Adelino F
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GENOTYPES , *PHENOTYPES , *DILATED cardiomyopathy , *FIBROSIS , *HEART failure - Abstract
Dilated cardiomyopathy (DCM) frequently affects relatively young, economically, and socially active adults, and is an important cause of heart failure and transplantation. DCM is a complex disease and its pathological architecture encounters many genetic determinants interacting with environmental factors. The old perspective that every pathogenic gene mutation would lead to a diseased heart, is now being replaced by the novel observation that the phenotype depends not only on the penetrance—malignancy of the mutated gene—but also on epigenetics, age, toxic factors, pregnancy, and a diversity of acquired diseases. This review discusses how gene mutations will result in mutation-specific molecular alterations in the heart including increased mitochondrial oxidation (sarcomeric gene e.g. TTN), decreased calcium sensitivity (sarcomeric genes), fibrosis (e.g. LMNA and TTN), or inflammation. Therefore, getting a complete picture of the DCM patient will include genomic data, molecular assessment by preference from cardiac samples, stratification according to co-morbidities, and phenotypic description. Those data will help to better guide the heart failure and anti-arrhythmic treatment, predict response to therapy, develop novel siRNA-based gene silencing for malignant gene mutations, or intervene with mutation-specific altered gene pathways in the heart. This article is part of the Mini Review Series from the Varenna 2017 meeting of the Working Group of Myocardial Function of the European Society of Cardiology. [ABSTRACT FROM AUTHOR]
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- 2018
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7. Implantable Cardioverter-Defibrillator in Dilated Cardiomyopathy after the DANISH-Trial Lesson. A Poly-Parametric Risk Evaluation Is Needed to Improve the Selection of Patients.
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Disertori, Marcello, Masè, Michela, Rigoni, Marta, Nollo, Giandomenico, Arbustini, Eloisa, and Ravelli, Flavia
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ELECTROTHERAPEUTICS equipment ,CARDIAC arrest prevention ,DILATED cardiomyopathy ,PATIENT acceptance of health care ,HEALTH outcome assessment ,THERAPEUTICS - Abstract
The article explores on the efficacy and safety of the implantable cardioverter-defibrillator (ICD) in reducing sudden cardiac death (SCD) in patients with non-ischemic dilated cardiomyopathy (DCM). It examines the medical protocols of symptomatic heart failure (HF). It also cites the assessment of ventricular fibrosis in the emergence of arrhythmogenic triggers in DCM patients.
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- 2017
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8. Genetic causes of dilated cardiomyopathy.
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Favalli, Valentina, Serio, Alessandra, Grasso, Maurizia, and Arbustini, Eloisa
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DILATED cardiomyopathy ,MEDICAL genetics ,GENETIC testing ,HISTOPATHOLOGY ,MOLECULAR diagnosis ,GENETICS ,ANIMALS ,DISEASE susceptibility ,GENETIC mutation ,PROGNOSIS ,PHENOTYPES ,GENETIC markers ,PREDICTIVE tests ,DIAGNOSIS ,THERAPEUTICS - Published
- 2016
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9. Left Ventricular Noncompaction: A Distinct Cardiomyopathy or a Trait Shared by Different Cardiac Diseases?
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Arbustini, Eloisa, Weidemann, Frank, and Hall, Jennifer L.
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CARDIOMYOPATHIES , *HEART diseases , *LEFT heart ventricle , *BIOMARKERS , *EPIDEMIOLOGY , *IMAGE analysis - Abstract
Whether left ventricular noncompaction (LVNC) is a distinct cardiomyopathy or a morphologic trait shared by different cardiomyopathies remains controversial. Current guidelines from professional organizations recommend different strategies for diagnosing and treating patients with LVNC. This state-of-the-art review discusses new insights into the basic mechanisms leading to LVNC, its clinical manifestations, treatment modalities, anatomy and pathology, embryology, genetics, epidemiology, and imaging. Three markers currently define LVNC: prominent left ventricular trabeculae, deep intertrabecular recesses, and a thin compacted layer. Although new genetic data from mice and humans supports LVNC as a distinct cardiomyopathy, evidence for LVNC as a shared morphological trait is not ruled out. Criteria supporting LVNC as a shared morphological trait may depend on consensus guidelines from the multiple professional organizations. Enhanced imaging and increased use of genetics are both predicted to significantly impact our overall understanding of the basic mechanisms causing LVNC and its optimal management. [ABSTRACT FROM AUTHOR]
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- 2014
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10. Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy
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Esslinger, Ulrike, Garnier, Sophie, Korniat, Agathe, Proust, Carole, Kararigas, Georgios, Müller-Nurasyid, Martina, Empana, Jean-Philippe, Morley, Michael P., Perret, Claire, Stark, Klaus, Bick, Alexander G., Prasad, Sanjay K., Kriebel, Jennifer, Li, Jin, Tiret, Laurence, Strauch, Konstantin, O'Regan, Declan P., Marguiles, Kenneth B., Seidman, Jonathan G., Boutouyrie, Pierre, Lacolley, Patrick, Jouven, Xavier, Hengstenberg, Christian, Komajda, Michel, Hakonarson, Hakon, Isnard, Richard, Arbustini, Eloisa, Grallert, Harald, Cook, Stuart A., Seidman, Christine E., Regitz-Zagrosek, Vera, Cappola, Thomas P., Charron, Philippe, Cambien, François, and Villard, Eric
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Biology and Life Sciences ,Genetics ,Genetic Loci ,Cell Biology ,Cell Processes ,Cellular Stress Responses ,Heat Shock Response ,Medicine and Health Sciences ,Cardiology ,Cardiomyopathies ,Pharmacology ,Drug Research and Development ,Drug Design ,Computer-Aided Drug Design ,Computational Biology ,Genome Analysis ,Genome-Wide Association Studies ,Genomics ,Human Genetics ,Precipitation Techniques ,Immunoprecipitation ,Co-Immunoprecipitation ,Biochemistry ,Proteins ,Chaperone Proteins ,Cellular Types ,Animal Cells ,Muscle Cells ,Myofibrils ,Sarcomeres ,Anatomy ,Biological Tissue ,Muscle Tissue - Abstract
Aims Dilated cardiomyopathy (DCM) is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS) to assess the contribution of missense variants to sporadic DCM. Methods and results 116,855 single nucleotide variants (SNVs) were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry. We confirmed two previously identified associations with SNVs in BAG3 and ZBTB17 and discovered six novel DCM-associated loci (Q-value<0.01). The lead-SNVs at novel loci are common and located in TTN, SLC39A8, MLIP, FLNC, ALPK3 and FHOD3. In silico fine mapping identified HSPB7 as the most likely candidate at the ZBTB17 locus. Rare variant analysis (MAF<0.01) demonstrated significant association for TTN variants only (P = 0.0085). All candidate genes but one (SLC39A8) exhibit preferential expression in striated muscle tissues and mutations in TTN, BAG3, FLNC and FHOD3 are known to cause familial cardiomyopathy. We also investigated a panel of 48 known cardiomyopathy genes. Collectively, rare (n = 228, P = 0.0033) or common (n = 36, P = 0.019) variants with elevated in silico severity scores were associated with DCM, indicating that the spectrum of genes contributing to sporadic DCM extends beyond those identified here. Conclusion: We identified eight loci independently associated with sporadic DCM. The functions of the best candidate genes at these loci suggest that proteostasis regulation might play a role in DCM pathophysiology.
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- 2017
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11. Electroanatomic Mapping and Late Gadolinium Enhancement MRI in a Genetic Model of Arrhythmogenic Atrial Cardiomyopathy.
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DISERTORI, MARCELLO, MASÈ, MICHELA, MARINI, MASSIMILIANO, MAZZOLA, SILVIA, CRISTOFORETTI, ALESSANDRO, DEL GRECO, MAURIZIO, KOTTKAMP, HANS, ARBUSTINI, ELOISA, and RAVELLI, FLAVIA
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FIBROSIS ,MAGNETIC resonance imaging ,ATRIAL arrhythmias ,BODY surface mapping ,ELECTROPHYSIOLOGY ,HEART atrium ,RESEARCH funding ,TOMOGRAPHY ,CONTRAST media ,DESCRIPTIVE statistics ,GENETICS ,DIAGNOSIS - Abstract
Evaluation of the Substrate in Genetic Atrial Arrhythmias Introduction Although atrial arrhythmias may have genetic causes, very few data are available on evaluation of the arrhythmic substrate in genetic atrial diseases in humans. In this study, we evaluate the nature and evolution of the atrial arrhythmic substrate in a genetic atrial cardiomyopathy. Methods and Results Repeated electroanatomic mapping and tomographic evaluations were used to investigate the evolving arrhythmic substrate in 5 patients with isolated arrhythmogenic atrial cardiomyopathy, caused by Natriuretic Peptide Precursor A ( NPPA) gene mutation. Atrial fibrosis was assessed using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). The substrate of atrial tachycardia (AT) and atrial fibrillation (AF) was biatrial dilatation with patchy areas of low voltage and atrial wall scarring (in the right atrium: 68.5% ± 6.0% and 22.2% ± 10.2%, respectively). The evolution of the arrhythmic patterns to sinus node disease with atrial standstill (AS) was associated with giant atria with extensive low voltage and atrial scarring areas (in the right atrium: 99.5% ± 0.7% and 57.5% ± 33.2%, respectively). LGE-MRI-proven biatrial fibrosis (Utah stage IV) was associated with AS. Atrial conduction was slow and heterogeneous, with lines of conduction blocks. The progressive extension and spatial distribution of the scarring/fibrosis were strictly associated with the different types of arrhythmias. Conclusion The evolution of the amount and distribution of atrial scarring/fibrosis constitutes the structural substrate for the different types of atrial arrhythmias in a pure genetic model of arrhythmogenic atrial cardiomyopathy. [ABSTRACT FROM AUTHOR]
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- 2014
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12. The MOGE(S) Classification of Cardiomyopathy for Clinicians.
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Arbustini, Eloisa, Narula, Navneet, Tavazzi, Luigi, Serio, Alessandra, Grasso, Maurizia, Favalli, Valentina, Bellazzi, Riccardo, Tajik, Jamil A., Bonow, Robert D., Fuster, Valentin, and Narula, Jagat
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CARDIOMYOPATHIES , *FAMILIAL diseases , *MEDICAL screening , *CARDIOLOGISTS , *NOSOLOGY , *PHENOTYPES - Abstract
Most cardiomyopathies are familial diseases. Cascade family screening identifies asymptomatic patients and family members with early traits of disease. The inheritance is autosomal dominant in a majority of cases, and recessive, X-linked, or matrilinear in the remaining. For the last 50 years, cardiomyopathy classifications have been based on the morphofunctional phenotypes, allowing cardiologists to conveniently group them in broad descriptive categories. However, the phenotype may not always conform to the genetic characteristics, may not allow risk stratification, and may not provide pre-clinical diagnoses in the family members. Because genetic testing is now increasingly becoming a part of clinical work-up, and based on the genetic heterogeneity, numerous new names are being coined for the description of cardiomyopathies associated with mutations in different genes; a comprehensive nosology is needed that could inform the clinical phenotype and involvement of organs other than the heart, as well as the genotype and the mode of inheritance. The recently proposed MOGE(S) nosology system embodies all of these characteristics, and describes the morphofunctional phenotype (M), organ(s) involvement (O), genetic inheritance pattern (G), etiological annotation (E) including genetic defect or underlying disease/substrate, and the functional status (S) of the disease using both the American College of Cardiology/American Heart Association stage and New York Heart Association functional class. The proposed nomenclature is supported by a web-assisted application and assists in the description of cardiomyopathy in symptomatic or asymptomatic patients and family members in the context of genetic testing. It is expected that such a nomenclature would help group cardiomyopathies on their etiological basis, describe complex genetics, and create collaborative registries. [ABSTRACT FROM AUTHOR]
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- 2014
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13. Fibrinogen.
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Arbustini, Eloisa, Narula, Nupoor, and D'Armini, Andrea M.
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FIBRINOGEN , *BLOOD coagulation factors , *BLOOD proteins , *THROMBOSIS , *BLOOD coagulation - Abstract
The author presents information on fibrinogen. Fibrinogen, or coagulation factor I, is a main player in thrombus formation. It is split by thrombin to form fibrin, which is the most abundant component of a blood clot. It is a proinflammatory factor in autoimmune and inflammatory diseases, such as rheumatoid arthritis, vasculitides, inflammatory bowel disease and multiple sclerosis.
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- 2013
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14. Autosomal Recessive Atrial Dilated Cardiomyopathy With Standstill Evolution Associated With Mutation of Natriuretic Peptide Precursor A.
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Disertori, Marcello, Quintarelli, Silvia, Grasso, Maurizia, Pilotto, Andrea, Narula, Nupoor, Favalli, Valentina, Canclini, Camilla, Diegoli, Marta, Mazzola, Silvia, Marini, Massimiliano, Del Greco, Maurizio, Bonmassari, Roberto, Masè, Michela, Ravelli, Flavia, Specchia, Claudia, and Arbustini, Eloisa
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Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983, we described 8-years follow-up of atrial dilatation with standstill evolution in 8 patients from 3 families. We later identified 5 additional patients with identical phenotypes: 1 member of the largest original family and 4 unrelated to the 3 original families. All families are from the same geographic area in Northeast Italy.We followed up the 13 patients for up to 37 years, extended the clinical investigation and monitoring to living relatives, and investigated the genetic basis of the disease. The disease was characterized by: (1) clinical onset in adulthood; (2) biatrial dilatation up to giant size; (3) early supraventricular arrhythmias with progressive loss of atrial electric activity to atrial standstill; (4) thromboembolic complications; and (5) stable, normal left ventricular function and New York Heart Association functional class during the long-term course of the disease. By linkage analysis, we mapped a locus at 1p36.22 containing the Natriuretic Peptide Precursor A gene. By sequencing Natriuretic Peptide Precursor A, we identified a homozygous missense mutation (p.Arg150Gln) in all living affected individuals of the 6 families. All patients showed low serum levels of atrial natriuretic peptide. Heterozygous mutation carriers were healthy and demonstrated normal levels of atrial natriuretic peptide.Autosomal recessive atrial dilated cardiomyopathy is a rare disease associated with homozygous mutation of the Natriuretic Peptide Precursor A gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function, and severely decreased levels of atrial natriuretic peptide. [ABSTRACT FROM AUTHOR]
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- 2013
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15. Extra-Aortic Identifiers to Guide Genetic Testing in Familial Thoracic Aortic Aneurysms and Dissections Syndromes: It Is All About the Company One Keeps ⁎ [⁎] Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
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Arbustini, Eloisa and Narula, Nupoor
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- 2012
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16. Mitochondrial DNA Variant Discovery and Evaluation in Human Cardiomyopathies through Next-Generation Sequencing.
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Zaragoza, Michael V., Fass, Joseph, Diegoli, Marta, Lin, Dawei, and Arbustini, Eloisa
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GENETIC mutation ,MITOCHONDRIAL DNA ,MITOCHONDRIAL pathology ,CARDIOMYOPATHIES ,HEART failure ,NUCLEOTIDE sequence ,GENETICS ,BIOLOGICAL variation ,GENETIC disorders - Abstract
Mutations in mitochondrial DNA (mtDNA) may cause maternally-inherited cardiomyopathy and heart failure. In homoplasmy all mtDNA copies contain the mutation. In heteroplasmy there is a mixture of normal and mutant copies of mtDNA. The clinical phenotype of an affected individual depends on the type of genetic defect and the ratios of mutant and normal mtDNA in affected tissues. We aimed at determining the sensitivity of next-generation sequencing compared to Sanger sequencing for mutation detection in patients with mitochondrial cardiomyopathy. We studied 18 patients with mitochondrial cardiomyopathy and two with suspected mitochondrial disease. We ''shotgun'' sequenced PCR-amplified mtDNA and multiplexed using a single run on Roche's 454 Genome Sequencer. By mapping to the reference sequence, we obtained 1,3006average coverage per case and identified high-confidence variants. By comparing these to >400 mtDNA substitution variants detected by Sanger, we found 98% concordance in variant detection. Simulation studies showed that >95% of the homoplasmic variants were detected at a minimum sequence coverage of 20× while heteroplasmic variants required >200× coverage. Several Sanger ''misses'' were detected by 454 sequencing. These included the novel heteroplasmic 7501T>C in tRNA serine 1 in a patient with sudden cardiac death. These results support a potential role of next-generation sequencing in the discovery of novel mtDNA variants with heteroplasmy below the level reliably detected with Sanger sequencing. We hope that this will assist in the identification of mtDNA mutations and key genetic determinants for cardiomyopathy and mitochondrial disease. [ABSTRACT FROM AUTHOR]
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- 2010
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17. Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects
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Arbustini, Eloisa, Pasotti, Michele, Pilotto, Andrea, Pellegrini, Carlo, Grasso, Maurizia, Previtali, Stefano, Repetto, Alessandra, Bellini, Ornella, Azan, Gaetano, Scaffino, Manuela, Campana, Carlo, Piccolo, Giovanni, Viganò, Mario, and Tavazzi, Luigi
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MUSCLE diseases , *CARDIOMYOPATHIES , *PHENOTYPES , *IMMUNOCYTOCHEMISTRY , *GENETICS - Abstract
Abstract: Background: Primary desminopathies are caused by desmin gene [DES (MIM*125660)] mutations. The clinical spectrum includes pure myopathies, cardiomuscular diseases and cardiomyopathies. Patients with restrictive cardiomyopathy (RCM) plus atrioventricular block (AVB) due to DES defects are frequently unrecognized unless desmin accumulation is specifically investigated in endomyocardial biopsy (EMB) by ultrastructural study. Aims: To describe a cardiological phenotype characterized by RCM plus AVB due to desmin accumulation caused by DES defects. Methods and results: Desmin accumulation was diagnosed by means of ultrastructural and immunocytochemical studies of EMB in four unrelated probands with RCM and AVB. Candidate genes [DES and αB-crystallin (CRYAB)] were screened using sequence analysis. Four DES gene mutations were identified: three new (R16C, T453I and a 10 bp deletion at the exon–intron boundary of exon 3 disrupting the donor splice site) and one known (R406W). The disease was autosomal dominant in two families, recessive in one and associated with a de novo mutation in one. The mutations cosegregated with phenotype in all patients. CRYAB gene screening was negative. Conclusions: A cardiac phenotype characterized by RCM and AVB caused by desmin accumulation is associated with DES mutations. Although the mutations affected different domains, the cardiac phenotype was identical. [Copyright &y& Elsevier]
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- 2006
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18. Left Ventricular Noncompaction A Distinct Cardiomyopathy or a Trait Shared by Different Cardiac Diseases?
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Arbustini, Eloisa, Weidemann, Frank, and Hall, Jennifer L.
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compacted ,trabeculae ,imaging ,epidemiology ,genetics ,pathology - Abstract
Whether left ventricular noncompaction (LVNC) is a distinct cardiomyopathy or a morphologic trait shared by different cardiomyopathies remains controversial. Current guidelines from professional organizations recommend different strategies for diagnosing and treating patients with LVNC. This state-of-the-art review discusses new insights into the basic mechanisms leading to LVNC, its clinical manifestations, treatment modalities, anatomy and pathology, embryology, genetics, epidemiology, and imaging. Three markers currently define LVNC: prominent left ventricular trabeculae, deep intertrabecular recesses, and a thin compacted layer. Although new genetic data from mice and humans supports LVNC as a distinct cardiomyopathy, evidence for LVNC as a shared morphological trait is not ruled out. Criteria supporting LVNC as a shared morphological trait may depend on consensus guidelines from the multiple professional organizations. Enhanced imaging and increased use of genetics are both predicted to significantly impact our overall understanding of the basic mechanisms causing LVNC and its optimal management.
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- View/download PDF
19. Extra-Aortic Identifiers to Guide Genetic Testing in Familial Thoracic Aortic Aneurysms and Dissections Syndromes It Is All About the Company One Keeps⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology
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Arbustini, Eloisa and Narula, Nupoor
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aorta ,cardiovascular system ,aneurysm ,genetics ,cerebrovascular disorders ,SMAD3 - Full Text
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20. POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking.
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Schindler, Roland F. R., Scotton, Chiara, Jianguo Zhang, Passarelli, Chiara, Ortiz-Bonnin, Beatriz, Simrick, Subreena, Schwerte, Thorsten, Kar-Lai Poon, Mingyan Fang, Rinné, Susanne, Froese, Alexander, Nikolaev, Viacheslav O., Grunert, Christiane, Müller, Thomas, Tasca, Giorgio, Sarathchandra, Padmini, Drago, Fabrizio, Dallapiccola, Bruno, Rapezzi, Claudio, and Arbustini, Eloisa
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ARRHYTHMIA , *MEMBRANE proteins , *MISSENSE mutation , *CYCLIC adenylic acid , *ACTION potentials , *GENETICS , *BIOLOGICAL transport , *MUSCULAR dystrophy , *GENETIC mutation , *RESEARCH funding ,MUSCULAR dystrophy genetics - Abstract
The Popeye domain-containing 1 (POPDC1) gene encodes a plasma membrane-localized cAMP-binding protein that is abundantly expressed in striated muscle. In animal models, POPDC1 is an essential regulator of structure and function of cardiac and skeletal muscle; however, POPDC1 mutations have not been associated with human cardiac and muscular diseases. Here, we have described a homozygous missense variant (c.602C>T, p.S201F) in POPDC1, identified by whole-exome sequencing, in a family of 4 with cardiac arrhythmia and limb-girdle muscular dystrophy (LGMD). This allele was absent in known databases and segregated with the pathological phenotype in this family. We did not find the allele in a further screen of 104 patients with a similar phenotype, suggesting this mutation to be family specific. Compared with WT protein, POPDC1(S201F) displayed a 50% reduction in cAMP affinity, and in skeletal muscle from patients, both POPDC1(S201F) and WT POPDC2 displayed impaired membrane trafficking. Forced expression of POPDC1(S201F) in a murine cardiac muscle cell line (HL-1) increased hyperpolarization and upstroke velocity of the action potential. In zebrafish, expression of the homologous mutation (popdc1(S191F)) caused heart and skeletal muscle phenotypes that resembled those observed in patients. Our study therefore identifies POPDC1 as a disease gene causing a very rare autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous group of inherited rare diseases. [ABSTRACT FROM AUTHOR]
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- 2016
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21. Diagnostic Work-Up and Risk Stratification in X-Linked Dilated Cardiomyopathies Caused by Dystrophin Defects
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Diegoli, Marta, Grasso, Maurizia, Favalli, Valentina, Serio, Alessandra, Gambarin, Fabiana Isabella, Klersy, Catherine, Pasotti, Michele, Agozzino, Emanuela, Scelsi, Laura, Ferlini, Alessandra, Febo, Oreste, Piccolo, Giovanni, Tavazzi, Luigi, Narula, Jagat, and Arbustini, Eloisa
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CARDIOMYOPATHIES , *HEALTH risk assessment , *X chromosome , *DYSTROPHIN genes , *GENETICS , *GENETIC mutation , *CONGESTIVE heart failure , *POLYMERASE chain reaction , *DIAGNOSIS - Abstract
Objectives: We sought to describe the diagnostic work-up, phenotype, and long-term evolution of dilated cardiomyopathy (DCM) associated with Dystrophin (DYS) defects. Background: X-linked DCM associated with DYS defects can be clinically indistinguishable from other types of DCM. Methods: The series comprises 436 consecutive male patients diagnosed with DCM. Patients underwent endomyocardial biopsy (EMB). Genetic testing employed multiplex polymerase chain reaction and multiple ligation dependent probe assay for deletions and direct sequencing of the 79 exons and flanking regions of the gene for point mutations or small rearrangements. Results: We identified DYS defects in 34 of 436 patients (7.8%) (onset age 34 ± 11 years, age range 17 to 54 years); 30 had proven X-linked inheritance. The 2 phenotypes included DCM with mild skeletal myopathy and/or increased serum creatine phosphokinase (n = 28) or DCM only (n = 6). The EMB showed defective dystrophin immunostain. The DYS defects consisted of 21 in-frame deletions and 11 out-of-frame deletions as well as 1 stop and 1 splice-site mutation. During a median follow-up of 60 months (interquartile range: 11.25 to 101.34 months) we observed 17 events, all related to heart failure (HF) (median event-free survival: 83.5 months). Eight patients (23%) underwent transplantation, and 9 (26%) died of HF while waiting for transplantation. Eight patients received an implantable cardioverter-defibrillator, although none had device intervention during a median follow-up of 14 months (interquartile range: 5 to 25 months). No patient died suddenly, suffered syncope, or developed life-threatening ventricular arrhythmias. Conclusions: DYS-related DCM should be suspected in male patients with increased serum creatine phosphokinase (82%) and X-linked inheritance. The disease shows a high risk of end-stage HF but a lower risk of life-threatening arrhythmias. [Copyright &y& Elsevier]
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- 2011
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22. Autosomal recessive atrial disease presenting with sick sinus syndrome (SSS), right atrial fibrosis and biatrial dilatation: Clinical impact of genetic diagnosis.
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De Regibus, Valentina, Rordorf, Roberto, Giorgianni, Carmelina, Canclini, Camilla, Vicentini, Alessandro, Taravelli, Erika, Petracci, Barbara, Savastano, Simone, De Servi, Stefano, and Arbustini, Eloisa
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SICK sinus syndrome , *SICK sinus syndrome treatment , *FIBROSIS , *GENETIC disorders , *DISEASE mapping , *CARDIAC research , *DIAGNOSIS , *THERAPEUTICS - Published
- 2016
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23. The shortness of Pygmies is associated with severe under-expression of the growth hormone receptor
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Bozzola, Mauro, Travaglino, Paola, Marziliano, Nicola, Meazza, Cristina, Pagani, Sara, Grasso, Maurizia, Tauber, Maithè, Diegoli, Marta, Pilotto, Andrea, Disabella, Eliana, Tarantino, Paolo, Brega, Agnese, and Arbustini, Eloisa
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HORMONE receptors , *SOMATOTROPIN , *GENE expression , *SHORT stature , *PYGMIES , *CAUCASIAN race , *ANTHROPOMETRY , *GENETICS - Abstract
Abstract: The stature is a highly heritable trait controlled by genetic and environmental factors. The African Pygmies represent a paradigmatic example of non-disease-related idiopathic short stature (ISS), showing a similar endocrine profile of Caucasian individuals with ISS. Pygmy children show normal anthropometric and endocrine parameters until puberty, while adult Pygmies show normal baseline and post-stimulation serum growth hormone (GH) levels but low values of baseline serum GH-binding protein (GHBP) and insulin-like growth factor-I (IGF-I). This discrepancy suggests a defective response to GH occurring in adulthood since Pygmies lack both the pubertal serum IGF-I surge and the growth spurt. However, sequencing of the key genes of the GH–IGF-I axis failed to identify Pygmy specific variants or haplotypes. We therefore aimed at assessing whether the quantitative gene expression profile of two key genes of the GH–IGF-I axis, GH and GHR, was also similar in low-stature and normal stature populations. We showed that the GH gene expression is 1.8-fold reduced and the GH receptor (GHR) gene expression is 8-fold reduced in adult Pygmies in comparison with sympatric adult Bantu, and that this reduction is not associated with sequence variants of the GHR gene. The marked decrease of the GHR expression in Pygmies is associated with reduced serum levels of the IGF-I and GHBP. Our results, documenting a markedly reduced GHR gene expression in adult Pygmies, could contribute to elucidate the mechanisms involved in ISS in Caucasoid subjects. [Copyright &y& Elsevier]
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- 2009
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24. Involvement of BAG3 and HSPB7 loci in various etiologies of systolic heart failure: Results of a European collaboration assembling more than 2000 patients.
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Garnier, Sophie, Hengstenberg, Christian, Lamblin, Nicolas, Dubourg, Olivier, De Groote, Pascal, Fauchier, Laurent, Trochu, Jean-Noël, Arbustini, Eloisa, Esslinger, Ulrike, Barton, Paul J., Meder, Benjamin, Katus, Hugo, Frese, Karen, Komajda, Michel, Cook, Stuart A., Isnard, Richard, Tiret, Laurence, Villard, Eric, and Charron, Philippe
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HEAT shock proteins , *HEART failure , *ETIOLOGY of diseases , *DILATED cardiomyopathy , *LOCUS (Genetics) - Published
- 2015
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25. Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial Function of the European Society of Cardiology
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Denise Hilfiker-Kleiner, Gilda Varricchi, Dana Dawson, Jolanda van der Velden, Stephane Heymans, Nazha Hamdani, Adelino F. Leite-Moreira, Anna Monica Bianco, Benjamin Meder, Carlo G. Tocchetti, Matteo De Rosa, Roddy Walsh, Michele Ciccarelli, Thomas Thum, Eloisa Arbustini, Antoine Bondue, Cardiologie, RS: CARIM - R2.02 - Cardiomyopathy, MUMC+: MA Med Staf Spec Cardiologie (9), Bondue, Antoine, Arbustini, Eloisa, Bianco, Anna, Ciccarelli, Michele, Dawson, Dana, De Rosa, Matteo, Hamdani, Nazha, Hilfiker-Kleiner, Denise, Meder, Benjamin, Leite Moreira, Adelino, Thum, Thoma, Tocchetti, Carlo G, Varricchi, Gilda, Van der Velden, Jolanda, Walsh, Roddy, and Heymans, Stephane
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0301 basic medicine ,Peripartum cardiomyopathy ,Physiology ,A/C GENE-MUTATIONS ,Genome-environment interaction ,Cardiomyopathy ,Genome-wide association study ,030204 cardiovascular system & hematology ,Gene mutation ,Review Series from the Varenna 2017 Meeting of Theworking Group of Myocardial Function of the European Society of Cardiology ,LMNA ,0302 clinical medicine ,PERIPARTUM CARDIOMYOPATHY ,Risk Factors ,DOXORUBICIN-INDUCED CARDIOMYOPATHY ,Ventricular Function ,MYOSIN HEAVY-CHAIN ,Dilated Cardiomyopathy ,HYPERTROPHIC CARDIOMYOPATHY ,Dilated cardiomyopathy ,ANTHRACYCLINE-INDUCED CARDIOTOXICITY ,Prognosis ,3. Good health ,Phenotype ,Cardiology ,Cardiology and Cardiovascular Medicine ,Cardiomyopathy, Dilated ,Sarcomeres ,RIGHT-VENTRICULAR CARDIOMYOPATHY ,medicine.medical_specialty ,Genetics ,03 medical and health sciences ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,CONGESTIVE-HEART-FAILURE ,business.industry ,Myocardium ,medicine.disease ,Myocardial Contraction ,Transplantation ,030104 developmental biology ,Heart failure ,Mutation ,Gene-Environment Interaction ,MOGE(S) CLASSIFICATION ,business - Abstract
Dilated cardiomyopathy (DCM) frequently affects relatively young, economically, and socially active adults, and is an important cause of heart failure and transplantation. DCM is a complex disease and its pathological architecture encounters many genetic determinants interacting with environmental factors. The old perspective that every pathogenic gene mutation would lead to a diseased heart, is now being replaced by the novel observation that the phenotype depends not only on the penetrance—malignancy of the mutated gene—but also on epigenetics, age, toxic factors, pregnancy, and a diversity of acquired diseases. This review discusses how gene mutations will result in mutation-specific molecular alterations in the heart including increased mitochondrial oxidation (sarcomeric gene e.g. TTN), decreased calcium sensitivity (sarcomeric genes), fibrosis (e.g. LMNA and TTN), or inflammation. Therefore, getting a complete picture of the DCM patient will include genomic data, molecular assessment by preference from cardiac samples, stratification according to co-morbidities, and phenotypic description. Those data will help to better guide the heart failure and anti-arrhythmic treatment, predict response to therapy, develop novel siRNA-based gene silencing for malignant gene mutations, or intervene with mutation-specific altered gene pathways in the heart. This article is part of the Mini Review Series from the Varenna 2017 meeting of the Working Group of Myocardial Function of the European Society of Cardiology.
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- 2018
26. Clinical pregenetic screening for stroke monogenic diseases: Results from lombardia GENS registry
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Giorgio Bono, Eloisa Arbustini, Patrizia Perrone, Silvia Baratta, Graziella Molini, Elena Pinuccia Verrengia, Massimiliano Braga, Manuel Corato, Erminio Capitani, Gaetano S. Grieco, Pierluigi Baron, Giampaolo Merlini, Simona Marcheselli, Giuseppe Micieli, Nadia Trobia, Davide Uccellini, Anna Cavallini, Elio Agostoni, Mario Guidotti, Carlo Ferrarese, Alessandro Padovani, Laura Fusi, Caspar Grond-Ginsbach, Giacomo P. Comi, Silvia Lanfranconi, Marco Arnaboldi, Barbara Incorvaia, Livia Candelise, Maria Teresa Bassi, Cristina Motto, Paola Carrera, Lorena Mosca, Nicoletta Checcarelli, Lucia Tancredi, Alessando Pezzini, Hugh S. Markus, Laura Obici, Giancarlo Comi, Bianca Maria Bordo, Maria Luisa De Lodovici, Giorgio B. Boncoraglio, Davide Zarcone, Maurizia Grasso, Dario Ronchi, Maria Sessa, Francesca Mazucchelli, Maria Vittoria Calloni, Stefania Corti, Francesco Sasanelli, Paolo Vitali, Giampiero Grampa, C. Gellera, Maurizio Ferrari, Cristina Cereda, Antonio Colombo, Silvana Penco, Anna Bersano, Franco Taroni, Simone Beretta, Carlo Sebastiano Tadeo, Silvana Quaglini, Eugenio Parati, Bersano, A, Markus, H, Quaglini, S, Arbustini, E, Lanfranconi, S, Micieli, G, Boncoraglio, G, Taroni, F, Gellera, C, Baratta, S, Penco, S, Mosca, L, Grasso, M, Carrera, P, Ferrari, M, Cereda, C, Grieco, G, Corti, S, Ronchi, D, Bassi, M, Obici, L, Parati, E, Pezzini, A, De Lodovici, M, Verrengia, E, Bono, G, Mazucchelli, F, Zarcone, D, Calloni, M, Perrone, P, Bordo, B, Colombo, A, Padovani, A, Cavallini, A, Beretta, S, Ferrarese, C, Motto, C, Agostoni, E, Molini, G, Sasanelli, F, Corato, M, Marcheselli, S, Sessa, M, Comi, G, Checcarelli, N, Guidotti, M, Uccellini, D, Capitani, E, Tancredi, L, Arnaboldi, M, Incorvaia, B, Tadeo, C, Fusi, L, Grampa, G, Merlini, G, Trobia, N, Braga, M, Vitali, P, Baron, P, Grond Ginsbach, C, Candelise, L, Bersano, Anna, Markus, Hugh Stephen, Quaglini, Silvana, Arbustini, Eloisa, Lanfranconi, Silvia, Micieli, Giuseppe, Boncoraglio, Giorgio B., Taroni, Franco, Gellera, Cinzia, Baratta, Silvia, Penco, Silvana, Mosca, Lorena, Grasso, Maurizia, Carrera, Paola, Ferrari, Maurizio, Cereda, Cristina, Grieco, Gaetano, Corti, Stefania, Ronchi, Dario, Bassi, Maria Teresa, Obici, Laura, Parati, Eugenio A., Pezzini, Alessando, De Lodovici, Maria Luisa, Verrengia, Elena P., Bono, Giorgio, Mazucchelli, Francesca, Zarcone, Davide, Calloni, Maria Vittoria, Perrone, Patrizia, Bordo, Bianca Maria, Colombo, Antonio, Padovani, Alessandro, Cavallini, Anna, Beretta, Simone, Ferrarese, Carlo, Motto, Cristina, Agostoni, Elio, Molini, Graziella, Sasanelli, Francesco, Corato, Manuel, Marcheselli, Simona, Sessa, Maria, Comi, Giancarlo, Checcarelli, Nicoletta, Guidotti, Mario, Uccellini, Davide, Capitani, Erminio, Tancredi, Lucia, Arnaboldi, Marco, Incorvaia, Barbara, Tadeo, Carlo Sebastiano, Fusi, Laura, Grampa, Giampiero, Merlini, Giampaolo, Trobia, Nadia, Comi, Giacomo Pietro, Braga, Massimiliano, Vitali, Paolo, Baron, Pierluigi, Grond Ginsbach, Caspar, and Candelise, Livia
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Adult ,Male ,Mitochondrial encephalomyopathy ,Pediatrics ,medicine.medical_specialty ,Pathology ,DNA Mutational Analysis ,CADASIL ,Disease ,030204 cardiovascular system & hematology ,MELAS syndrome ,Leukoencephalopathy ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,genetics ,Genetic Testing ,Registries ,Stroke ,cerebral amyloid angiopathy ,Aged ,Genetic testing ,Advanced and Specialized Nursing ,Fabry disease ,medicine.diagnostic_test ,business.industry ,cerebral amyloid angiopathy, familial ,Marfan syndrome ,stroke ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,familial ,Middle Aged ,medicine.disease ,Mutation ,Female ,genetic ,business ,030217 neurology & neurosurgery - Abstract
Background and Purpose— Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease Methods— We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of Results— In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease. Conclusions— In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.
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- 2016
27. Molecular reclassification of Crohn's disease: a cautionary note on population stratification
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Emmanuelle Génin, Jean-Pierre Hugot, Bärbel Maus, Kristel Van Steen, Jestinah M. Mahachie John, Camille Jung, and Arbustini, Eloisa
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Adult ,Male ,Adolescent ,Genotype ,Population ,Population genetics ,lcsh:Medicine ,Single-nucleotide polymorphism ,Ancestry-informative marker ,Biology ,Population stratification ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Crohn Disease ,Genetic predisposition ,Cluster Analysis ,Humans ,Genetic Predisposition to Disease ,education ,lcsh:Science ,030304 developmental biology ,Genetics ,0303 health sciences ,education.field_of_study ,Principal Component Analysis ,Multidisciplinary ,Confounding ,lcsh:R ,Genetic marker ,030211 gastroenterology & hepatology ,lcsh:Q ,Female ,Research Article - Abstract
Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn's disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn's disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals. ispartof: PLoS One vol:8 issue:10 ispartof: location:United States status: published
- Published
- 2013
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