Search

Your search keyword '"Mazzarotto, Francesco"' showing total 176 results
Start Over Author "Mazzarotto, Francesco"
176 results on '"Mazzarotto, Francesco"'

1. Exploring the complex spectrum of dominance and recessiveness in genetic cardiomyopathies.

Author

Lipov, Alex, Jurgens, Sean, Mazzarotto, Francesco, Allouba, Mona, Aguib, Yasmine, Gennarelli, Massimo, Yacoub, Magdi, Ellinor, Patrick, Bezzina, Connie, Walsh, Roddy, and Pirruccello, James

Subjects
Cardiovascular genetics, Genetics research, Medical genetics, Medical genomics
Abstract

Discrete categorization of Mendelian disease genes into dominant and recessive models often oversimplifies their underlying genetic architecture. Cardiomyopathies (CMs) are genetic diseases with complex etiologies for which an increasing number of recessive associations have recently been proposed. Here, we comprehensively analyze all published evidence pertaining to biallelic variation associated with CM phenotypes to identify high-confidence recessive genes and explore the spectrum of monoallelic and biallelic variant effects in established recessive and dominant disease genes. We classify 18 genes with robust recessive association with CMs, largely characterized by dilated phenotypes, early disease onset and severe outcomes. Several of these genes have monoallelic association with disease outcomes and cardiac traits in the UK Biobank, including LMOD2 and ALPK3 with dilated and hypertrophic CM, respectively. Our data provide insights into the complex spectrum of dominance and recessiveness in genetic heart disease and demonstrate how such approaches enable the discovery of unexplored genetic associations.

Published
2023

2. Genetic determinants of coping, resilience and self-esteem in schizophrenia suggest a primary role for social factors and hippocampal neurogenesis

Author

Caulo, Chiara, D'Agostino, Giulia, Corrivetti, Giulio, Selvaggi, Pierluigi, D'Ambrosio, Enrico, Di Palo, Piergiuseppe, Atti, Anna Rita, Barlati, Stefano, Ceraso, Anna, Nibbio, Gabriele, Paribello, Pasquale, Marras, Luca, Carpiniello, Bernardo, Piegari, Giuseppe, Giordano, Giulia Maria, Pezzella, Pasquale, Melillo, Antonio, Concerto, Carmen, Mineo, Ludovico, Pettorruso, Mauro, Chiappini, Stefania, Di Carlo, Francesco, Altamura, Mario, Leccisotti, Ivana, De Masi, Laura, Calcagno, Pietro, Serafini, Gianluca, Arzani, Costanza, Di Stefano, Ramona, Pacitti, Francesca, Rossi, Rodolfo, Giusti, Laura, Mammarella, Silvia, Vecchio, Sasha Del, Marcatili, Matteo, Fusi, Oscar, Gramaglia, Carla, Marangon, Debora, Bestagini, Lucia, Meneguzzo, Paolo, Tenconi, Elena, Favaro, Angela, Gerra, Maria Lidia, Borelli, Davide Fausto, Magnani, Francesca, Carpita, Barbara, Cremone, Ivan Mirko, Amatori, Giulia, Buzzanca, Antonino, Frascarelli, Marianna, Accinni, Tommaso, Berardelli, Isabella, Erbuto, Denise, Comparelli, Anna, Cuomo, Alessandro, Goracci, Arianna, Bolognesi, Simone, Niolu, Cinzia, Di Lorenzo, Giorgio, Jannini, Tommaso, Brasso, Claudio, Villari, Vincenzo, Sgro, Rodolfo, Mazzarotto, Francesco, Monteleone, Palmiero, Minelli, Alessandra, Mattevi, Stefania, Cascino, Giammarco, Rocca, Paola, Rossi, Alessandro, Bertolino, Alessandro, Aguglia, Eugenio, Altamura, Carlo, Amore, Mario, Bellomo, Antonello, Bucci, Paola, Collantoni, Enrico, Dell'Osso, Liliana, Di Fabio, Fabio, Fagiolini, Andrea, Giuliani, Luigi, Marchesi, Carlo, Martinotti, Giovanni, Montemagni, Cristiana, Pinna, Federica, Pompili, Maurizio, Rampino, Antonio, Roncone, Rita, Siracusano, Alberto, Vita, Antonio, Zeppegno, Patrizia, Galderisi, Silvana, Gennarelli, Massimo, and Maj, Mario

Published
2024
Full Text
View/download PDF

4. Evidence-Based Assessment of Genes in Dilated Cardiomyopathy

Author

Jordan, Elizabeth, Peterson, Laiken, Ai, Tomohiko, Asatryan, Babken, Bronicki, Lucas, Brown, Emily, Celeghin, Rudy, Edwards, Matthew, Fan, Judy, Ingles, Jodie, James, Cynthia A, Jarinova, Olga, Johnson, Renee, Judge, Daniel P, Lahrouchi, Najim, Deprez, Ronald H Lekanne, Lumbers, R Thomas, Mazzarotto, Francesco, Domingo, Argelia Medeiros, Miller, Rebecca L, Morales, Ana, Murray, Brittney, Peters, Stacey, Pilichou, Kalliopi, Protonotarios, Alexandros, Semsarian, Christopher, Shah, Palak, Syrris, Petros, Thaxton, Courtney, van Tintelen, J Peter, Walsh, Roddy, Wang, Jessica, Ware, James, and Hershberger, Ray E

Subjects
Cardiovascular, Genetics, Heart Disease, Rare Diseases, Biotechnology, Cardiomyopathy, Dilated, Evidence-Based Medicine, Expert Testimony, Genetic Predisposition to Disease, Genetic Testing, Humans, cardiomyopathy, genetics, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundEach of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted.MethodsAn international panel with clinical and scientific expertise in DCM genetics evaluated evidence supporting monogenic relationships of genes with idiopathic DCM. The panel used the Clinical Genome Resource semiquantitative gene-disease clinical validity classification framework with modifications for DCM genetics to classify genes into categories on the basis of the strength of currently available evidence. Representation of DCM genes on clinically available genetic testing panels was evaluated.ResultsFifty-one genes with human genetic evidence were curated. Twelve genes (23%) from 8 gene ontologies were classified as having definitive (BAG3, DES, FLNC, LMNA, MYH7, PLN, RBM20, SCN5A, TNNC1, TNNT2, TTN) or strong (DSP) evidence. Seven genes (14%; ACTC1, ACTN2, JPH2, NEXN, TNNI3, TPM1, VCL) including 2 additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of these 19 genes, 6 were similarly classified for hypertrophic cardiomyopathy and 3 for arrhythmogenic right ventricular cardiomyopathy. Of the remaining 32 genes (63%), 25 (49%) had limited evidence, 4 (8%) were disputed, 2 (4%) had no disease relationship, and 1 (2%) was supported by animal model data only. Of the 16 evaluated clinical genetic testing panels, most definitive genes were included, but panels also included numerous genes with minimal human evidence.ConclusionsIn the curation of 51 genes, 19 had high evidence (12 definitive/strong, 7 moderate). It is notable that these 19 genes explain only a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed. Clinical genetic testing panels include most high-evidence genes; however, genes lacking robust evidence are also commonly included. We recommend that high-evidence DCM genes be used for clinical practice and that caution be exercised in the interpretation of variants in variable-evidence DCM genes.

Published
2021

5. Slower Calcium Handling Balances Faster Crossbridge Cycling in Human MYBPC3 HCM

Author

Pioner, Josè Manuel, Vitale, Giulia, Steczina, Sonette, Langione, Marianna, Margara, Francesca, Santini, Lorenzo, Giardini, Francesco, Lazzeri, Erica, Piroddi, Nicoletta, Scellini, Beatrice, Palandri, Chiara, Schuldt, Maike, Spinelli, Valentina, Girolami, Francesca, Mazzarotto, Francesco, van der Velden, Jolanda, Cerbai, Elisabetta, Tesi, Chiara, Olivotto, Iacopo, Bueno-Orovio, Alfonso, Sacconi, Leonardo, Coppini, Raffaele, Ferrantini, Cecilia, Regnier, Michael, and Poggesi, Corrado

Published
2023
Full Text
View/download PDF

6. Phenotypic Expression and Outcomes in Individuals With Rare Genetic Variants of Hypertrophic Cardiomyopathy

Author

de Marvao, Antonio, McGurk, Kathryn A., Zheng, Sean L., Thanaj, Marjola, Bai, Wenjia, Duan, Jinming, Biffi, Carlo, Mazzarotto, Francesco, Statton, Ben, Dawes, Timothy J.W., Savioli, Nicolò, Halliday, Brian P., Xu, Xiao, Buchan, Rachel J., Baksi, A. John, Quinlan, Marina, Tokarczuk, Paweł, Tayal, Upasana, Francis, Catherine, Whiffin, Nicola, Theotokis, Pantazis I., Zhang, Xiaolei, Jang, Mikyung, Berry, Alaine, Pantazis, Antonis, Barton, Paul J.R., Rueckert, Daniel, Prasad, Sanjay K., Walsh, Roddy, Ho, Carolyn Y., Cook, Stuart A., Ware, James S., and O’Regan, Declan P.

Published
2021
Full Text
View/download PDF

7. Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation

Author

Thompson, Andrea D., Helms, Adam S., Kannan, Anamika, Yob, Jaime, Lakdawala, Neal K., Wittekind, Samuel G., Pereira, Alexandre C., Jacoby, Daniel L., Colan, Steven D., Ashley, Euan A., Saberi, Sara, Ware, James S., Ingles, Jodie, Semsarian, Christopher, Michels, Michelle, Mazzarotto, Francesco, Olivotto, Iacopo, Ho, Carolyn Y., and Day, Sharlene M.

Published
2021
Full Text
View/download PDF

8. Characterization of the genetic architecture of dilated cardiomyopathy using families and cohorts

Author

Mazzarotto, Francesco, Cook, Stuart, and Barton, Paul

Subjects
616.1
Abstract

Cardiomyopathies are the leading cause of heart transplantation in the developed world, and dilated cardiomyopathy accounts for an important proportion of all heart failure cases in large clinical trials. In spite of a strong genetic basis for dilated cardiomyopathy being demonstrated widely in the past two decades, 60% of familial cases remain unexplained. Dilated cardiomyopathy is characterized by marked genetic heterogeneity, with more than 60 individual genes reported to cause the disease, yet only one (TTN) explaining more than 10% of cases. Here, high-throughput sequencing data, advanced imaging techniques and bioinformatics analyses were used to dissect the genetic architecture of dilated cardiomyopathy, by measuring the contribution of single genes and multi-genic variation on disease risk and severity, and performing gene and variant discovery in affected families. Burden testing (using bespoke software developed in the R programming language for this study) and regression modelling were used to examine the genetic determinants of disease by comparing a cohort of disease cases (n=332) to ethnically matched, phenotypically characterised healthy controls (n=319). This produced a measure of the contribution of each gene to dilated cardiomyopathy, taking into account the background variation rate in the general population. Analyses of multi-genic interactions were also performed, and having detected the signature of additive effects of variation in multiple genes on both disease likelihood and severity, further analyses were performed to identify specific gene-gene interactions in causing dilated cardiomyopathy. Subsequently, variant prioritisation strategies were developed to identify, from whole-exome sequencing data, possible genetic causes of an unexplained and very severe form of early-onset dilated cardiomyopathy segregating in a family. This led to the identification of new candidate genes, which might contribute towards a genetic diagnosis in the analysed family and to new insights into the pathogenesis of dilated cardiomyopathy. Preparatory work in developing variant prioritisation pipelines from whole-exome sequencing data had been performed earlier, on families affected with various inherited arrhythmia syndromes.

Published
2016
Full Text
View/download PDF

9. Systematic large-scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies

Author

Mazzarotto, Francesco, Hawley, Megan H., Beltrami, Matteo, Beekman, Leander, de Marvao, Antonio, McGurk, Kathryn A., Statton, Ben, Boschi, Beatrice, Girolami, Francesca, Roberts, Angharad M., Lodder, Elisabeth M., Allouba, Mona, Romeih, Soha, Aguib, Yasmine, Baksi, A. John, Pantazis, Antonis, Prasad, Sanjay K., Cerbai, Elisabetta, Yacoub, Magdi H., O’Regan, Declan P., Cook, Stuart A., Ware, James S., Funke, Birgit, Olivotto, Iacopo, Bezzina, Connie R., Barton, Paul J. R., and Walsh, Roddy

Published
2021
Full Text
View/download PDF

10. Ion channel dysfunction and fibrosis in atrial fibrillation: Two sides of the same coin

Author

Arabia, Gianmarco, primary, Bellicini, Maria Giulia, additional, Cersosimo, Angelica, additional, Memo, Maurizio, additional, Mazzarotto, Francesco, additional, Inciardi, Riccardo Maria, additional, Cerini, Manuel, additional, Chen, Lin Yee, additional, Aboelhassan, Mohamed, additional, Benzoni, Patrizia, additional, Mitacchione, Gianfranco, additional, Bontempi, Luca, additional, and Curnis, Antonio, additional

Published
2024
Full Text
View/download PDF

11. Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect

Author

Tadros, Rafik, Francis, Catherine, Xu, Xiao, Vermeer, Alexa M. C., Harper, Andrew R., Huurman, Roy, Kelu Bisabu, Ken, Walsh, Roddy, Hoorntje, Edgar T., te Rijdt, Wouter P., Buchan, Rachel J., van Velzen, Hannah G., van Slegtenhorst, Marjon A., Vermeulen, Jentien M., Offerhaus, Joost Allard, Bai, Wenjia, de Marvao, Antonio, Lahrouchi, Najim, Beekman, Leander, Karper, Jacco C., Veldink, Jan H., Kayvanpour, Elham, Pantazis, Antonis, Baksi, A. John, Whiffin, Nicola, Mazzarotto, Francesco, Sloane, Geraldine, Suzuki, Hideaki, Schneider-Luftman, Deborah, Elliott, Paul, Richard, Pascale, Ader, Flavie, Villard, Eric, Lichtner, Peter, Meitinger, Thomas, Tanck, Michael W. T., van Tintelen, J. Peter, Thain, Andrew, McCarty, David, Hegele, Robert A., Roberts, Jason D., Amyot, Julie, Dubé, Marie-Pierre, Cadrin-Tourigny, Julia, Giraldeau, Geneviève, L’Allier, Philippe L., Garceau, Patrick, Tardif, Jean-Claude, Boekholdt, S. Matthijs, Lumbers, R. Thomas, Asselbergs, Folkert W., Barton, Paul J. R., Cook, Stuart A., Prasad, Sanjay K., O’Regan, Declan P., van der Velden, Jolanda, Verweij, Karin J. H., Talajic, Mario, Lettre, Guillaume, Pinto, Yigal M., Meder, Benjamin, Charron, Philippe, de Boer, Rudolf A., Christiaans, Imke, Michels, Michelle, Wilde, Arthur A. M., Watkins, Hugh, Matthews, Paul M., Ware, James S., and Bezzina, Connie R.

Published
2021
Full Text
View/download PDF

12. Defining the diagnostic effectiveness of genes for inclusion in panels: the experience of two decades of genetic testing for hypertrophic cardiomyopathy at a single center

Author

Mazzarotto, Francesco, Girolami, Francesca, Boschi, Beatrice, Barlocco, Fausto, Tomberli, Alessia, Baldini, Katia, Coppini, Raffaele, Tanini, Ilaria, Bardi, Sara, Contini, Elisa, Cecchi, Franco, Pelo, Elisabetta, Cook, Stuart A., Cerbai, Elisabetta, Poggesi, Corrado, Torricelli, Francesca, Walsh, Roddy, and Olivotto, Iacopo

Published
2019
Full Text
View/download PDF

13. A gene-centric strategy for identifying disease-causing rare variants in dilated cardiomyopathy

Author

Horvat, Claire, Johnson, Renee, Lam, Lien, Munro, Jacob, Mazzarotto, Francesco, Roberts, Angharad M., Herman, Daniel S., Parfenov, Michael, Haghighi, Alireza, McDonough, Barbara, DePalma, Steven R., Keogh, Anne M., Macdonald, Peter S., Hayward, Christopher S., Roberts, Amy, Barton, Paul J. R., Felkin, Leanne E., Giannoulatou, Eleni, Cook, Stuart A., Seidman, J. G., Seidman, Christine E., and Fatkin, Diane

Published
2019
Full Text
View/download PDF

15. Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: the case of hypertrophic cardiomyopathy

Author

Walsh, Roddy, Mazzarotto, Francesco, Whiffin, Nicola, Buchan, Rachel, Midwinter, William, Wilk, Alicja, Li, Nicholas, Felkin, Leanne, Ingold, Nathan, Govind, Risha, Ahmad, Mian, Mazaika, Erica, Allouba, Mona, Zhang, Xiaolei, de Marvao, Antonio, Day, Sharlene M., Ashley, Euan, Colan, Steven D., Michels, Michelle, Pereira, Alexandre C., Jacoby, Daniel, Ho, Carolyn Y., Thomson, Kate L., Watkins, Hugh, Barton, Paul J. R., Olivotto, Iacopo, Cook, Stuart A., and Ware, James S.

Published
2019
Full Text
View/download PDF

16. Abstract 14781: Computational Prediction of Protein Subdomain Stability as a Novel Approach to Cardiac Myosin Binding ProteinC Variant Adjudication and Clinical Risk Stratification in Hypertrophic Cardiomyopathy

Author

Thompson, Andrea D, Helms, Adam S, Kannan, Anamika, Yob, Jaime, Lakdawala, Neal K, Wittekind, Samuel, Pereira, Alexandre D, Jacoby, Daniel L, Colan, Steven D, Saberi, Sara, Ware, James S, Ingles, Jodie, Semsarian, Christopher, Michels, Michelle, Mazzarotto, Francesco, olivotto, iacopo, Ho, Carolyn, and Day, Sharlene

Published
2020
Full Text
View/download PDF

18. Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy

Author

Mazzarotto, Francesco, Tayal, Upasana, Buchan, Rachel J., Midwinter, William, Wilk, Alicja, Whiffin, Nicola, Govind, Risha, Mazaika, Erica, de Marvao, Antonio, Dawes, Timothy J.W., Felkin, Leanne E., Ahmad, Mian, Theotokis, Pantazis I., Edwards, Elizabeth, Ing, Alexander Y., Thomson, Kate L., Chan, Laura L.H., Sim, David, Baksi, A. John, Pantazis, Antonis, Roberts, Angharad M., Watkins, Hugh, Funke, Birgit, O’Regan, Declan P., Olivotto, Iacopo, Barton, Paul J.R., Prasad, Sanjay K., Cook, Stuart A., Ware, James S., and Walsh, Roddy

Published
2020
Full Text
View/download PDF

19. Slower Calcium Handling Balances Faster Cross-Bridge Cycling in Human MYBPC3 HCM

Author

Pioner, Josè Manuel, primary, Vitale, Giulia, additional, Steczina, Sonette, additional, Langione, Marianna, additional, Margara, Francesca, additional, Santini, Lorenzo, additional, Giardini, Francesco, additional, Lazzeri, Erica, additional, Piroddi, Nicoletta, additional, Scellini, Beatrice, additional, Palandri, Chiara, additional, Schuldt, Maike, additional, Spinelli, Valentina, additional, Girolami, Francesca, additional, Mazzarotto, Francesco, additional, van der Velden, Jolanda, additional, Cerbai, Elisabetta, additional, Tesi, Chiara, additional, Olivotto, Iacopo, additional, Bueno-Orovio, Alfonso, additional, Sacconi, Leonardo, additional, Coppini, Raffaele, additional, Ferrantini, Cecilia, additional, Regnier, Michael, additional, and Poggesi, Corrado, additional

Published
2023
Full Text
View/download PDF

20. 1152 INVESTIGATION ON THE HIGH INCIDENCE OF THE ATTRV-CAUSING TRANSTHYRETIN VARIANT VAL142ILE IN CENTRAL ITALY

Author

Cappelli, Francesco, primary, Argiro´, Alessia, additional, Zampieri, Mattia, additional, Giotti, Irene, additional, Boschi, Beatrice, additional, Frusconi, Sabrina, additional, Buxbaum, Joel, additional, Gennarelli, Massimo, additional, Polimanti, Renato, additional, Olivotto, Iacopo, additional, Perfetto, Federico, additional, and Mazzarotto, Francesco, additional

Published
2022
Full Text
View/download PDF

21. Investigation on the high recurrence of the ATTRv-causing transthyretin variant Val142Ile in central Italy

Author

Mazzarotto, Francesco, primary, Argirò, Alessia, additional, Zampieri, Mattia, additional, Magri, Chiara, additional, Giotti, Irene, additional, Boschi, Beatrice, additional, Frusconi, Sabrina, additional, Gennarelli, Massimo, additional, Buxbaum, Joel, additional, Polimanti, Renato, additional, Olivotto, Iacopo, additional, Perfetto, Federico, additional, and Cappelli, Francesco, additional

Published
2022
Full Text
View/download PDF

22. Calcium handling maturation and adaptation to increased substrate stiffness in human iPSC-derived cardiomyocytes: The impact of full-length dystrophin deficiency

Author

Pioner, Josè Manuel, primary, Santini, Lorenzo, additional, Palandri, Chiara, additional, Langione, Marianna, additional, Grandinetti, Bruno, additional, Querceto, Silvia, additional, Martella, Daniele, additional, Mazzantini, Costanza, additional, Scellini, Beatrice, additional, Giammarino, Lucrezia, additional, Lupi, Flavia, additional, Mazzarotto, Francesco, additional, Gowran, Aoife, additional, Rovina, Davide, additional, Santoro, Rosaria, additional, Pompilio, Giulio, additional, Tesi, Chiara, additional, Parmeggiani, Camilla, additional, Regnier, Michael, additional, Cerbai, Elisabetta, additional, Mack, David L., additional, Poggesi, Corrado, additional, Ferrantini, Cecilia, additional, and Coppini, Raffaele, additional

Published
2022
Full Text
View/download PDF

23. Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death

Author

Walsh, Roddy, Adler, Arnon, Amin, Ahmad S, Abiusi, Emanuela, Care, Melanie, Bikker, Hennie, Amenta, Simona, Feilotter, Harriet, Nannenberg, Eline A, Mazzarotto, Francesco, Trevisan, Valentina, Garcia, John, Hershberger, Ray E, Perez, Marco V, Sturm, Amy C, Ware, James S, Zareba, Wojciech, Novelli, Valeria, Wilde, Arthur A M, Gollob, Michael H, Abiusi, Emanuela (ORCID:0000-0001-9028-012X), Walsh, Roddy, Adler, Arnon, Amin, Ahmad S, Abiusi, Emanuela, Care, Melanie, Bikker, Hennie, Amenta, Simona, Feilotter, Harriet, Nannenberg, Eline A, Mazzarotto, Francesco, Trevisan, Valentina, Garcia, John, Hershberger, Ray E, Perez, Marco V, Sturm, Amy C, Ware, James S, Zareba, Wojciech, Novelli, Valeria, Wilde, Arthur A M, Gollob, Michael H, and Abiusi, Emanuela (ORCID:0000-0001-9028-012X)

Abstract

Aims Catecholaminergic polymorphic ventricular tachycardia (CPVT) and short QT syndrome (SQTS) are inherited arrhythmogenic disorders that can cause sudden death. Numerous genes have been reported to cause these conditions, but evidence supporting these gene-disease relationships varies considerably. To ensure appropriate utilization of genetic information for CPVT and SQTS patients, we applied an evidence-based reappraisal of previously reported genes. Methods and results Three teams independently curated all published evidence for 11 CPVT and 9 SQTS implicated genes using the ClinGen gene curation framework. The results were reviewed by a Channelopathy Expert Panel who provided the final classifications. Seven genes had definitive to moderate evidence for disease causation in CPVT, with either autosomal dominant (RYR2, CALM1, CALM2, CALM3) or autosomal recessive (CASQ2, TRDN, TECRL) inheritance. Three of the four disputed genes for CPVT (KCNJ2, PKP2, SCN5A) were deemed by the Expert Panel to be reported for phenotypes that were not representative of CPVT, while reported variants in a fourth gene (ANK2) were too common in the population to be disease-causing. For SQTS, only one gene (KCNH2) was classified as definitive, with three others (KCNQ1, KCNJ2, SLC4A3) having strong to moderate evidence. The majority of genetic evidence for SQTS genes was derived from very few variants (five in KCNJ2, two in KCNH2, one in KCNQ1/SLC4A3). Conclusions Seven CPVT and four SQTS genes have valid evidence for disease causation and should be included in genetic testing panels. Additional genes associated with conditions that may mimic clinical features of CPVT/SQTS have potential utility for differential diagnosis.

Published
2022

24. Disease Progression of Hypertrophic Cardiomyopathy: Modeling Using Machine Learning

Author

Pičulin, Matej, primary, Smole, Tim, additional, Žunkovič, Bojan, additional, Kokalj, Enja, additional, Robnik-Šikonja, Marko, additional, Kukar, Matjaž, additional, Fotiadis, Dimitrios I, additional, Pezoulas, Vasileios C, additional, Tachos, Nikolaos S, additional, Barlocco, Fausto, additional, Mazzarotto, Francesco, additional, Popović, Dejana, additional, Maier, Lars S, additional, Velicki, Lazar, additional, Olivotto, Iacopo, additional, MacGowan, Guy A, additional, Jakovljević, Djordje G, additional, Filipović, Nenad, additional, and Bosnić, Zoran, additional

Published
2022
Full Text
View/download PDF

25. Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD

Author

Garrett, Alice, primary, Loveday, Chey, additional, King, Laura, additional, Butler, Samantha, additional, Robinson, Rachel, additional, Horton, Carrie, additional, Yussuf, Amal, additional, Choi, Subin, additional, Torr, Beth, additional, Durkie, Miranda, additional, Burghel, George J., additional, Drummond, James, additional, Berry, Ian, additional, Wallace, Andrew, additional, Callaway, Alison, additional, Eccles, Diana, additional, Tischkowitz, Marc, additional, Tatton-Brown, Katrina, additional, Snape, Katie, additional, McVeigh, Terri, additional, Izatt, Louise, additional, Woodward, Emma R., additional, Burnichon, Nelly, additional, Gimenez-Roqueplo, Anne-Paule, additional, Mazzarotto, Francesco, additional, Whiffin, Nicola, additional, Ware, James, additional, Hanson, Helen, additional, Pesaran, Tina, additional, LaDuca, Holly, additional, Buffet, Alexandre, additional, Maher, Eamonn R., additional, and Turnbull, Clare, additional

Published
2022
Full Text
View/download PDF

26. Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies

Author

Ware, James S., Li, Jian, Mazaika, Erica, Yasso, Christopher M., DeSouza, Tiffany, Cappola, Thomas P., Tsai, Emily J., Hilfiker-Kleiner, Denise, Kamiya, Chizuko A., Mazzarotto, Francesco, Cook, Stuart A., Halder, Indrani, Prasad, Sanjay K., Pisarcik, Jessica, Hanley-Yanez, Karen, Alharethi, Rami, Damp, Julie, Hsich, Eileen, Elkayam, Uri, Sheppard, Richard, Kealey, Angela, Alexis, Jeffrey, Ramani, Gautam, Safirstein, Jordan, Boehmer, John, Pauly, Daniel F., Wittstein, Ilan S., Thohan, Vinay, Zucker, Mark J., Liu, Peter, Gorcsan, John, III, McNamara, Dennis M., Seidman, Christine E., Seidman, Jonathan G., and Arany, Zoltan

Published
2016
Full Text
View/download PDF

27. Genetic determinants of coping, resilience and self-esteem in schizophrenia suggest a primary role for social factors and hippocampal neurogenesis.

Author

Mazzarotto, Francesco, Monteleone, Palmiero, Minelli, Alessandra, Mattevi, Stefania, Cascino, Giammarco, Rocca, Paola, Rossi, Alessandro, Bertolino, Alessandro, Aguglia, Eugenio, Altamura, Carlo, Amore, Mario, Bellomo, Antonello, Bucci, Paola, Collantoni, Enrico, Dell'Osso, Liliana, Di Fabio, Fabio, Fagiolini, Andrea, Giuliani, Luigi, Marchesi, Carlo, and Martinotti, Giovanni

Subjects
*GENOME-wide association studies, *GENETIC variation, *LIPID metabolism, *MENTAL illness, *NEUROTICISM
Abstract

• Resilience, coping and self-esteem are outcome predictors in schizophrenia (SCZ). • A GWAS on 490 SCZ patients characterized with 4 dedicated scales was performed. • Sixteen loci emerge as (at least suggestively) associated with these scales. • There is genetic overlap with SCZ itself, neuroticism and worry. • Social-, hippocampal- and lipid-related aspects appear generally relevant. Schizophrenia is a severe psychiatric disorder, associated with a reduction in life expectancy of 15–20 years. Available treatments are at least partially effective in most affected individuals, and personal resources such as resilience (successful adaptation despite adversity) and coping abilities (strategies used to deal with stressful or threatening situations), are important determinants of disease outcomes and long-term sustained recovery. Published findings support the existence of a genetic background underlying resilience and coping, with variable heritability estimates. However, genome-wide analyses concerning the genetic determinants of these personal resources, especially in the context of schizophrenia, are lacking. Here, we performed a genome-wide association study coupled with accessory analyses to investigate potential genetic determinants of resilience, coping and self-esteem in 490 schizophrenia patients. Results revealed a complex genetic background partly overlapping with that of neuroticism, worry and schizophrenia itself and support the importance of social aspects in shapingthese psychological constructs. Hippocampal neurogenesis and lipid metabolism appear to be potentially relevant biological underpinnings, and specific miRNAs such as miR-124 and miR-137 may warrant further studies as potential biomarkers. In conclusion, this study represents an important first step in the identification of genetic and biological correlates shaping resilience, coping resources and self-esteem in schizophrenia. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

28. Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death

Author

Walsh, Roddy, primary, Adler, Arnon, additional, Amin, Ahmad S, additional, Abiusi, Emanuela, additional, Care, Melanie, additional, Bikker, Hennie, additional, Amenta, Simona, additional, Feilotter, Harriet, additional, Nannenberg, Eline A, additional, Mazzarotto, Francesco, additional, Trevisan, Valentina, additional, Garcia, John, additional, Hershberger, Ray E, additional, Perez, Marco V, additional, Sturm, Amy C, additional, Ware, James S, additional, Zareba, Wojciech, additional, Novelli, Valeria, additional, Wilde, Arthur A M, additional, and Gollob, Michael H, additional

Published
2021
Full Text
View/download PDF

29. A machine learning-based risk stratification model for ventricular tachycardia and heart failure in hypertrophic cardiomyopathy

Author

Smole, Tim, primary, Žunkovič, Bojan, additional, Pičulin, Matej, additional, Kokalj, Enja, additional, Robnik-Šikonja, Marko, additional, Kukar, Matjaž, additional, Fotiadis, Dimitrios I., additional, Pezoulas, Vasileios C., additional, Tachos, Nikolaos S., additional, Barlocco, Fausto, additional, Mazzarotto, Francesco, additional, Popović, Dejana, additional, Maier, Lars, additional, Velicki, Lazar, additional, MacGowan, Guy A., additional, Olivotto, Iacopo, additional, Filipović, Nenad, additional, Jakovljević, Djordje G., additional, and Bosnić, Zoran, additional

Published
2021
Full Text
View/download PDF

30. Arrhythmogenic potential of myocardial disarray in hypertrophic cardiomyopathy: genetic basis, functional consequences and relation to sudden cardiac death

Author

Finocchiaro, Gherardo, primary, Sheikh, Nabeel, additional, Leone, Ornella, additional, Westaby, Joe, additional, Mazzarotto, Francesco, additional, Pantazis, Antonis, additional, Ferrantini, Cecilia, additional, Sacconi, Leonardo, additional, Papadakis, Michael, additional, Sharma, Sanjay, additional, Sheppard, Mary N, additional, and Olivotto, Iacopo, additional

Published
2021
Full Text
View/download PDF

31. Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls

Author

Walsh, Roddy, Lahrouchi, Najim, Tadros, Rafik, Kyndt, Florence, Glinge, Charlotte, Postema, Pieter G., Amin, Ahmad S., Nannenberg, Eline A., Ware, James S., Whiffin, Nicola, Mazzarotto, Francesco, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, Bos, J. Martijn, Breckpot, Jeroen, Campuzano, Oscar, Castelletti, Silvia, Celen, Candan, Clauss, Sebastian, Corveleyn, Anniek, Crotti, Lia, Dagradi, Federica, de Asmundis, Carlo, Denjoy, Isabelle, Dittmann, Sven, Ellinor, Patrick T., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen K., Kimoto, Hiroki, Kotta, Maria-Christina, Krapels, Ingrid P. C., Kurabayashi, Masahiko, Lazarte, Julieta, Leenhardt, Antoine, Loeys, Bart L., Lundin, Catarina, Makiyama, Takeru, Mansourati, Jacques, Martins, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, Sahin, Hatice, Sarquella-Brugada, Georgia, Sebastiano, Regina, Sharma, Sanjay, Sheppard, Mary N., Shimamoto, Keiko, Shoemaker, M. Benjamin, Stallmeyer, Birgit, Steinfurt, Johannes, Tanaka, Yuji, Tester, David J., Usuda, Keisuke, van der Zwaag, Paul A., Van Dooren, Sonia, Van Laer, Lut, Winbo, Annika, Winkel, Bo G., Yamagata, Kenichiro, Zumhagen, Sven, Volders, Paul G. A., Lubitz, Steven A., Antzelevitch, Charles, Platonov, Pyotr G., Odening, Katja E., Roden, Dan M., Roberts, Jason D., Skinner, Jonathan R., Tfelt-Hansen, Jacob, van den Berg, Maarten P., Olesen, Morten S., Lambiase, Pier D., Borggrefe, Martin, Hayashi, Kenshi, Rydberg, Annika, Nakajima, Tadashi, Yoshinaga, Masao, Saenen, Johan B., Kaeaeb, Stefan, Brugada, Pedro, Robyns, Tomas, Giachino, Daniela F., Ackerman, Michael J., Brugada, Ramon, Brugada, Josep, Gimeno, Juan R., Hasdemir, Can, Guicheney, Pascale, Priori, Silvia G., Schulze-Bahr, Eric, Makita, Naomasa, Schwartz, Peter J., Shimizu, Wataru, Aiba, Takeshi, Schott, Jean-Jacques, Redon, Richard, Ohno, Seiko, Probst, Vincent, Behr, Elijah R., Barc, Julien, Bezzina, Connie R., Walsh, Roddy, Lahrouchi, Najim, Tadros, Rafik, Kyndt, Florence, Glinge, Charlotte, Postema, Pieter G., Amin, Ahmad S., Nannenberg, Eline A., Ware, James S., Whiffin, Nicola, Mazzarotto, Francesco, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, Bos, J. Martijn, Breckpot, Jeroen, Campuzano, Oscar, Castelletti, Silvia, Celen, Candan, Clauss, Sebastian, Corveleyn, Anniek, Crotti, Lia, Dagradi, Federica, de Asmundis, Carlo, Denjoy, Isabelle, Dittmann, Sven, Ellinor, Patrick T., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen K., Kimoto, Hiroki, Kotta, Maria-Christina, Krapels, Ingrid P. C., Kurabayashi, Masahiko, Lazarte, Julieta, Leenhardt, Antoine, Loeys, Bart L., Lundin, Catarina, Makiyama, Takeru, Mansourati, Jacques, Martins, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, Sahin, Hatice, Sarquella-Brugada, Georgia, Sebastiano, Regina, Sharma, Sanjay, Sheppard, Mary N., Shimamoto, Keiko, Shoemaker, M. Benjamin, Stallmeyer, Birgit, Steinfurt, Johannes, Tanaka, Yuji, Tester, David J., Usuda, Keisuke, van der Zwaag, Paul A., Van Dooren, Sonia, Van Laer, Lut, Winbo, Annika, Winkel, Bo G., Yamagata, Kenichiro, Zumhagen, Sven, Volders, Paul G. A., Lubitz, Steven A., Antzelevitch, Charles, Platonov, Pyotr G., Odening, Katja E., Roden, Dan M., Roberts, Jason D., Skinner, Jonathan R., Tfelt-Hansen, Jacob, van den Berg, Maarten P., Olesen, Morten S., Lambiase, Pier D., Borggrefe, Martin, Hayashi, Kenshi, Rydberg, Annika, Nakajima, Tadashi, Yoshinaga, Masao, Saenen, Johan B., Kaeaeb, Stefan, Brugada, Pedro, Robyns, Tomas, Giachino, Daniela F., Ackerman, Michael J., Brugada, Ramon, Brugada, Josep, Gimeno, Juan R., Hasdemir, Can, Guicheney, Pascale, Priori, Silvia G., Schulze-Bahr, Eric, Makita, Naomasa, Schwartz, Peter J., Shimizu, Wataru, Aiba, Takeshi, Schott, Jean-Jacques, Redon, Richard, Ohno, Seiko, Probst, Vincent, Behr, Elijah R., Barc, Julien, and Bezzina, Connie R.

Abstract

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.

Published
2021
Full Text
View/download PDF

32. A machine learning-based risk stratification model for ventricular tachycardia and heart failure in hypertrophic cardiomyopathy

Author

Smole, Tim, Smole, Tim, Žunkovič, Bojan, Pičulin, Matej, Kokalj, Enja, Robnik-Šikonja, Marko, Kukar, Matjaž, Fotiadis, Dimitrios I., Pezoulas, Vasileios C., Tachos, Nikolaos S., Barlocco, Fausto, Mazzarotto, Francesco, Popović, Dejana, Maier, Lars, Velicki, Lazar, MacGowan, Guy A., Olivotto, Iacopo, Filipović, Nenad, Jakovljević, Đorđe G., Bosnić, Zoran, Smole, Tim, Smole, Tim, Žunkovič, Bojan, Pičulin, Matej, Kokalj, Enja, Robnik-Šikonja, Marko, Kukar, Matjaž, Fotiadis, Dimitrios I., Pezoulas, Vasileios C., Tachos, Nikolaos S., Barlocco, Fausto, Mazzarotto, Francesco, Popović, Dejana, Maier, Lars, Velicki, Lazar, MacGowan, Guy A., Olivotto, Iacopo, Filipović, Nenad, Jakovljević, Đorđe G., and Bosnić, Zoran

Abstract

Background: Machine learning (ML) and artificial intelligence are emerging as important components of precision medicine that enhance diagnosis and risk stratification. Risk stratification tools for hypertrophic cardiomyopathy (HCM) exist, but they are based on traditional statistical methods. The aim was to develop a novel machine learning risk stratification tool for the prediction of 5-year risk in HCM. The goal was to determine if its predictive accuracy is higher than the accuracy of the state-of-the-art tools. Method: Data from a total of 2302 patients were used. The data were comprised of demographic characteristics, genetic data, clinical investigations, medications, and disease-related events. Four classification models were applied to model the risk level, and their decisions were explained using the SHAP (SHapley Additive exPlanations) method. Unwanted cardiac events were defined as sustained ventricular tachycardia occurrence (VT), heart failure (HF), ICD activation, sudden cardiac death (SCD), cardiac death, and all-cause death. Results: The proposed machine learning approach outperformed the similar existing risk-stratification models for SCD, cardiac death, and all-cause death risk-stratification: it achieved higher AUC by 17%, 9%, and 1%, respectively. The boosted trees achieved the best performing AUC of 0.82. The resulting model most accurately predicts VT, HF, and ICD with AUCs of 0.90, 0.88, and 0.87, respectively. Conclusions: The proposed risk-stratification model demonstrates high accuracy in predicting events in patients with hypertrophic cardiomyopathy. The use of a machine-learning risk stratification model may improve patient management, clinical practice, and outcomes in general.

Published
2021

33. Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect

Author

Neurologen, Brain, Genetica, Circulatory Health, Onderzoek Vrouw Hart & Vaatziekten, Team Medisch, Tadros, Rafik, Francis, Catherine, Xu, Xiao, Vermeer, Alexa M.C., Harper, Andrew R., Huurman, Roy, Kelu Bisabu, Ken, Walsh, Roddy, Hoorntje, Edgar T., te Rijdt, Wouter P., Buchan, Rachel J., van Velzen, Hannah G., van Slegtenhorst, Marjon A., Vermeulen, Jentien M., Offerhaus, Joost Allard, Bai, Wenjia, de Marvao, Antonio, Lahrouchi, Najim, Beekman, Leander, Karper, Jacco C., Veldink, Jan H., Kayvanpour, Elham, Pantazis, Antonis, Baksi, A. John, Whiffin, Nicola, Mazzarotto, Francesco, Sloane, Geraldine, Suzuki, Hideaki, Schneider-Luftman, Deborah, Elliott, Paul, Richard, Pascale, Ader, Flavie, Villard, Eric, Lichtner, Peter, Meitinger, Thomas, Tanck, Michael W.T., van Tintelen, J. Peter, Thain, Andrew, McCarty, David, Hegele, Robert A., Roberts, Jason D., Amyot, Julie, Dubé, Marie Pierre, Cadrin-Tourigny, Julia, Giraldeau, Geneviève, L’Allier, Philippe L., Garceau, Patrick, Tardif, Jean Claude, Boekholdt, S. Matthijs, Lumbers, R. Thomas, Asselbergs, Folkert W., Barton, Paul J.R., Cook, Stuart A., Prasad, Sanjay K., O’Regan, Declan P., van der Velden, Jolanda, Verweij, Karin J.H., Talajic, Mario, Lettre, Guillaume, Pinto, Yigal M., Meder, Benjamin, Charron, Philippe, de Boer, Rudolf A., Christiaans, Imke, Michels, Michelle, Wilde, Arthur A.M., Watkins, Hugh, Matthews, Paul M., Ware, James S., Bezzina, Connie R., Neurologen, Brain, Genetica, Circulatory Health, Onderzoek Vrouw Hart & Vaatziekten, Team Medisch, Tadros, Rafik, Francis, Catherine, Xu, Xiao, Vermeer, Alexa M.C., Harper, Andrew R., Huurman, Roy, Kelu Bisabu, Ken, Walsh, Roddy, Hoorntje, Edgar T., te Rijdt, Wouter P., Buchan, Rachel J., van Velzen, Hannah G., van Slegtenhorst, Marjon A., Vermeulen, Jentien M., Offerhaus, Joost Allard, Bai, Wenjia, de Marvao, Antonio, Lahrouchi, Najim, Beekman, Leander, Karper, Jacco C., Veldink, Jan H., Kayvanpour, Elham, Pantazis, Antonis, Baksi, A. John, Whiffin, Nicola, Mazzarotto, Francesco, Sloane, Geraldine, Suzuki, Hideaki, Schneider-Luftman, Deborah, Elliott, Paul, Richard, Pascale, Ader, Flavie, Villard, Eric, Lichtner, Peter, Meitinger, Thomas, Tanck, Michael W.T., van Tintelen, J. Peter, Thain, Andrew, McCarty, David, Hegele, Robert A., Roberts, Jason D., Amyot, Julie, Dubé, Marie Pierre, Cadrin-Tourigny, Julia, Giraldeau, Geneviève, L’Allier, Philippe L., Garceau, Patrick, Tardif, Jean Claude, Boekholdt, S. Matthijs, Lumbers, R. Thomas, Asselbergs, Folkert W., Barton, Paul J.R., Cook, Stuart A., Prasad, Sanjay K., O’Regan, Declan P., van der Velden, Jolanda, Verweij, Karin J.H., Talajic, Mario, Lettre, Guillaume, Pinto, Yigal M., Meder, Benjamin, Charron, Philippe, de Boer, Rudolf A., Christiaans, Imke, Michels, Michelle, Wilde, Arthur A.M., Watkins, Hugh, Matthews, Paul M., Ware, James S., and Bezzina, Connie R.

Published
2021

34. Evidence-Based Assessment of Genes in Dilated Cardiomyopathy

Author

Arts-assistenten Kinderen, Genetica, Circulatory Health, Jordan, Elizabeth, Peterson, Laiken, Ai, Tomohiko, Asatryan, Babken, Bronicki, Lucas, Brown, Emily, Celeghin, Rudy, Edwards, Matthew, Fan, Judy, Ingles, Jodie, James, Cynthia A, Jarinova, Olga, Johnson, Renee, Judge, Daniel P, Lahrouchi, Najim, Lekanne Deprez, Ronald H, Lumbers, R Thomas, Mazzarotto, Francesco, Medeiros Domingo, Argelia, Miller, Rebecca L, Morales, Ana, Murray, Brittney, Peters, Stacey, Pilichou, Kalliopi, Protonotarios, Alexandros, Semsarian, Christopher, Shah, Palak, Syrris, Petros, Thaxton, Courtney, van Tintelen, J Peter, Walsh, Roddy, Wang, Jessica, Ware, James, Hershberger, Ray E, Arts-assistenten Kinderen, Genetica, Circulatory Health, Jordan, Elizabeth, Peterson, Laiken, Ai, Tomohiko, Asatryan, Babken, Bronicki, Lucas, Brown, Emily, Celeghin, Rudy, Edwards, Matthew, Fan, Judy, Ingles, Jodie, James, Cynthia A, Jarinova, Olga, Johnson, Renee, Judge, Daniel P, Lahrouchi, Najim, Lekanne Deprez, Ronald H, Lumbers, R Thomas, Mazzarotto, Francesco, Medeiros Domingo, Argelia, Miller, Rebecca L, Morales, Ana, Murray, Brittney, Peters, Stacey, Pilichou, Kalliopi, Protonotarios, Alexandros, Semsarian, Christopher, Shah, Palak, Syrris, Petros, Thaxton, Courtney, van Tintelen, J Peter, Walsh, Roddy, Wang, Jessica, Ware, James, and Hershberger, Ray E

Published
2021

36. Disease Progression of Hypertrophic Cardiomyopathy: Modeling Using Machine Learning (Preprint)

Author

Pičulin, Matej, primary, Smole, Tim, additional, Žunkovič, Bojan, additional, Kokalj, Enja, additional, Robnik-Šikonja, Marko, additional, Kukar, Matjaž, additional, Fotiadis, Dimitrios I, additional, Pezoulas, Vasileios C, additional, Tachos, Nikolaos S, additional, Barlocco, Fausto, additional, Mazzarotto, Francesco, additional, Popović, Dejana, additional, Maier, Lars S, additional, Velicki, Lazar, additional, Olivotto, Iacopo, additional, MacGowan, Guy A, additional, Jakovljević, Djordje G, additional, Filipović, Nenad, additional, and Bosnić, Zoran, additional

Published
2021
Full Text
View/download PDF

37. Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes amongst UK Biobank participants

Author

de Marvao, Antonio, primary, McGurk, Kathryn A, additional, Zheng, Sean L, additional, Thanaj, Marjola, additional, Bai, Wenjia, additional, Duan, Jinming, additional, Biffi, Carlo, additional, Mazzarotto, Francesco, additional, Statton, Ben, additional, Dawes, Timothy JW, additional, Savioli, Nicolò, additional, Halliday, Brian P, additional, Xu, Xiao, additional, Buchan, Rachel J, additional, Baksi, A John, additional, Quinlan, Marina, additional, Tokarczuk, Paweł, additional, Tayal, Upasana, additional, Francis, Catherine, additional, Whiffin, Nicola, additional, Theotokis, Pantazis I, additional, Zhang, Xiaolei, additional, Jang, Mikyung, additional, Berry, Alaine, additional, Pantazis, Antonis, additional, Barton, Paul JR, additional, Rueckert, Daniel, additional, Prasad, Sanjay K, additional, Walsh, Roddy, additional, Ho, Carolyn Y, additional, Cook, Stuart A, additional, Ware, James S, additional, and O’Regan, Declan P, additional

Published
2021
Full Text
View/download PDF

38. Disease-specific variant pathogenicity prediction significantly improves variant interpretation in inherited cardiac conditions

Author

Zhang, Xiaolei, primary, Walsh, Roddy, additional, Whiffin, Nicola, additional, Buchan, Rachel, additional, Midwinter, William, additional, Wilk, Alicja, additional, Govind, Risha, additional, Li, Nicholas, additional, Ahmad, Mian, additional, Mazzarotto, Francesco, additional, Roberts, Angharad, additional, Theotokis, Pantazis I., additional, Mazaika, Erica, additional, Allouba, Mona, additional, de Marvao, Antonio, additional, Pua, Chee Jian, additional, Day, Sharlene M., additional, Ashley, Euan, additional, Colan, Steven D., additional, Michels, Michelle, additional, Pereira, Alexandre C., additional, Jacoby, Daniel, additional, Ho, Carolyn Y., additional, Olivotto, Iacopo, additional, Gunnarsson, Gunnar T., additional, Jefferies, John L., additional, Semsarian, Chris, additional, Ingles, Jodie, additional, O’Regan, Declan P., additional, Aguib, Yasmine, additional, Yacoub, Magdi H., additional, Cook, Stuart A., additional, Barton, Paul J.R., additional, Bottolo, Leonardo, additional, and Ware, James S., additional

Published
2021
Full Text
View/download PDF

39. Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls

Author

Walsh, Roddy, primary, Lahrouchi, Najim, additional, Tadros, Rafik, additional, Kyndt, Florence, additional, Glinge, Charlotte, additional, Postema, Pieter G., additional, Amin, Ahmad S., additional, Nannenberg, Eline A., additional, Ware, James S., additional, Whiffin, Nicola, additional, Mazzarotto, Francesco, additional, Škorić-Milosavljević, Doris, additional, Krijger, Christian, additional, Arbelo, Elena, additional, Babuty, Dominique, additional, Barajas-Martinez, Hector, additional, Beckmann, Britt M., additional, Bézieau, Stéphane, additional, Bos, J. Martijn, additional, Breckpot, Jeroen, additional, Campuzano, Oscar, additional, Castelletti, Silvia, additional, Celen, Candan, additional, Clauss, Sebastian, additional, Corveleyn, Anniek, additional, Crotti, Lia, additional, Dagradi, Federica, additional, de Asmundis, Carlo, additional, Denjoy, Isabelle, additional, Dittmann, Sven, additional, Ellinor, Patrick T., additional, Ortuño, Cristina Gil, additional, Giustetto, Carla, additional, Gourraud, Jean-Baptiste, additional, Hazeki, Daisuke, additional, Horie, Minoru, additional, Ishikawa, Taisuke, additional, Itoh, Hideki, additional, Kaneko, Yoshiaki, additional, Kanters, Jørgen K., additional, Kimoto, Hiroki, additional, Kotta, Maria-Christina, additional, Krapels, Ingrid P.C., additional, Kurabayashi, Masahiko, additional, Lazarte, Julieta, additional, Leenhardt, Antoine, additional, Loeys, Bart L., additional, Lundin, Catarina, additional, Makiyama, Takeru, additional, Mansourati, Jacques, additional, Martins, Raphaël P., additional, Mazzanti, Andrea, additional, Mörner, Stellan, additional, Napolitano, Carlo, additional, Ohkubo, Kimie, additional, Papadakis, Michael, additional, Rudic, Boris, additional, Molina, Maria Sabater, additional, Sacher, Frédéric, additional, Sahin, Hatice, additional, Sarquella-Brugada, Georgia, additional, Sebastiano, Regina, additional, Sharma, Sanjay, additional, Sheppard, Mary N., additional, Shimamoto, Keiko, additional, Shoemaker, M.Benjamin, additional, Stallmeyer, Birgit, additional, Steinfurt, Johannes, additional, Tanaka, Yuji, additional, Tester, David J., additional, Usuda, Keisuke, additional, van der Zwaag, Paul A., additional, Van Dooren, Sonia, additional, Van Laer, Lut, additional, Winbo, Annika, additional, Winkel, Bo G., additional, Yamagata, Kenichiro, additional, Zumhagen, Sven, additional, Volders, Paul G.A., additional, Lubitz, Steven A., additional, Antzelevitch, Charles, additional, Platonov, Pyotr G., additional, Odening, Katja E., additional, Roden, Dan M., additional, Roberts, Jason D., additional, Skinner, Jonathan R., additional, Tfelt-Hansen, Jacob, additional, van den Berg, Maarten P., additional, Olesen, Morten S., additional, Lambiase, Pier D., additional, Borggrefe, Martin, additional, Hayashi, Kenshi, additional, Rydberg, Annika, additional, Nakajima, Tadashi, additional, Yoshinaga, Masao, additional, Saenen, Johan B., additional, Kääb, Stefan, additional, Brugada, Pedro, additional, Robyns, Tomas, additional, Giachino, Daniela F., additional, Ackerman, Michael J., additional, Brugada, Ramon, additional, Brugada, Josep, additional, Gimeno, Juan R., additional, Hasdemir, Can, additional, Guicheney, Pascale, additional, Priori, Silvia G., additional, Schulze-Bahr, Eric, additional, Makita, Naomasa, additional, Schwartz, Peter J., additional, Shimizu, Wataru, additional, Aiba, Takeshi, additional, Schott, Jean-Jacques, additional, Redon, Richard, additional, Ohno, Seiko, additional, Probst, Vincent, additional, Arnaout, Alain Al, additional, Amelot, Mathieu, additional, Anselme, Frédéric, additional, Billon, Olivier, additional, Defaye, Pascal, additional, Dupuis, Jean-Marc, additional, Jesel, Laurence, additional, Laurent, Gabriel, additional, Maury, Philippe, additional, Pasquie, Jean-Luc, additional, Wiart, Francois, additional, Behr, Elijah R., additional, Barc, Julien, additional, and Bezzina, Connie R., additional

Published
2021
Full Text
View/download PDF

40. An Evidence-based Assessment of Genes in Dilated Cardiomyopathy

Author

Jordan, Elizabeth, primary, Peterson, Laiken, additional, Ai, Tomohiko, additional, Asatryan, Babken, additional, Bronicki, Lucas, additional, Brown, Emily, additional, Celeghin, Rudy, additional, Edwards, Matthew, additional, Fan, Judy, additional, Ingles, Jodie, additional, James, Cynthia A, additional, Jarinova, Olga, additional, Johnson, Renee, additional, Judge, Daniel P, additional, Lahrouchi, Najim, additional, Deprez, Ronald Lekanne, additional, Lumbers, R Thomas, additional, Mazzarotto, Francesco, additional, Domingo, Argelia Medeiros, additional, Miller, Rebecca, additional, Morales, Ana, additional, Murray, Brittney, additional, Peters, Stacey, additional, Pilichou, Kalliopi, additional, Protonotarios, Alexandros, additional, Semsarian, Christopher, additional, Shah, Palak, additional, Syrris, Petros, additional, Thaxton, Courtney, additional, van Tintelen, J Peter, additional, Walsh, Roddy, additional, Wang, Jessica, additional, Ware, James, additional, and Hershberger, Ray E, additional

Published
2020
Full Text
View/download PDF

41. Sex-related differences in exercise performance and outcome of patients with hypertrophic cardiomyopathy

Author

Ghiselli, Luca, primary, Marchi, Alberto, additional, Fumagalli, Carlo, additional, Maurizi, Niccolò, additional, Oddo, Andrea, additional, Pieri, Francesco, additional, Girolami, Francesca, additional, Rowin, Ethan, additional, Mazzarotto, Francesco, additional, Cicoira, Mariantonietta, additional, Ribichini, Flavio, additional, Arretini, Anna, additional, Targetti, Mattia, additional, Passantino, Silvia, additional, Cecchi, Franco, additional, Marchionni, Niccolò, additional, Maron, Martin, additional, Mori, Fabio, additional, and Olivotto, Iacopo, additional

Published
2020
Full Text
View/download PDF

42. Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy

Author

Helms, Adam S., primary, Thompson, Andrea D., additional, Glazier, Amelia A., additional, Hafeez, Neha, additional, Kabani, Samat, additional, Rodriguez, Juliani, additional, Yob, Jaime M., additional, Woolcock, Helen, additional, Mazzarotto, Francesco, additional, Lakdawala, Neal K., additional, Wittekind, Samuel G., additional, Pereira, Alexandre C., additional, Jacoby, Daniel L., additional, Colan, Steven D., additional, Ashley, Euan A., additional, Saberi, Sara, additional, Ware, James S., additional, Ingles, Jodie, additional, Semsarian, Christopher, additional, Michels, Michelle, additional, Olivotto, Iacopo, additional, Ho, Carolyn Y., additional, and Day, Sharlene M., additional

Published
2020
Full Text
View/download PDF

44. Disease-specific variant pathogenicity prediction significantly improves variant interpretation in inherited cardiac conditions

Author

Zhang, Xiaolei, primary, Walsh, Roddy, additional, Whiffin, Nicola, additional, Buchan, Rachel, additional, Midwinter, William, additional, Wilk, Alicja, additional, Govind, Risha, additional, Li, Nicholas, additional, Ahmad, Mian, additional, Mazzarotto, Francesco, additional, Roberts, Angharad, additional, Theotokis, Pantazis, additional, Mazaika, Erica, additional, Allouba, Mona, additional, de Marvao, Antonio, additional, Pua, Chee Jian, additional, Day, Sharlene M, additional, Ashley, Euan, additional, Colan, Steven D, additional, Michels, Michelle, additional, Pereira, Alexandre C, additional, Jacoby, Daniel, additional, Ho, Carolyn Y, additional, Olivotto, Iacopo, additional, Gunnarsson, Gunnar T, additional, Jefferies, John, additional, Semsarian, Chris, additional, Ingles, Jodie, additional, O’Regan, Declan P., additional, Aguib, Yasmine, additional, Yacoub, Magdi H., additional, Cook, Stuart A., additional, Barton, Paul J.R., additional, Bottolo, Leonardo, additional, and Ware, James S., additional

Published
2020
Full Text
View/download PDF

46. The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases

Author

Mazzarotto, Francesco, primary, Hawley, Megan H., additional, Beltrami, Matteo, additional, Beekman, Leander, additional, de Marvao, Antonio, additional, McGurk, Kathryn A., additional, Statton, Ben, additional, Boschi, Beatrice, additional, Girolami, Francesca, additional, Roberts, Angharad M., additional, Lodder, Elisabeth M., additional, Allouba, Mona, additional, Romeih, Soha, additional, Aguib, Yasmine, additional, Baksi, A. John, additional, Pantazis, Antonis, additional, Prasad, Sanjay K., additional, Cerbai, Elisabetta, additional, Yacoub, Magdi H., additional, O’Regan, Declan P., additional, Cook, Stuart A., additional, Ware, James S., additional, Funke, Birgit, additional, Olivotto, Iacopo, additional, Bezzina, Connie R., additional, Barton, Paul J.R., additional, and Walsh, Roddy, additional

Published
2020
Full Text
View/download PDF

47. Additional file 2: of Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: the case of hypertrophic cardiomyopathy

Author

Walsh, Roddy, Mazzarotto, Francesco, Whiffin, Nicola, Buchan, Rachel, Midwinter, William, Wilk, Alicja, Li, Nicholas, Felkin, Leanne, Ingold, Nathan, Risha Govind, Ahmad, Mian, Mazaika, Erica, Allouba, Mona, Xiaolei Zhang, Marvao, Antonio, Day, Sharlene, Ashley, Euan, Colan, Steven, Michels, Michelle, Pereira, Alexandre, Jacoby, Daniel, Ho, Carolyn, Thomson, Kate, Watkins, Hugh, Barton, Paul, Olivotto, Iacopo, Cook, Stuart, and Ware, James

Abstract

Supplementary figures S1 and S2. (DOCX 742 kb)

Published
2019
Full Text
View/download PDF

48. 121 Re-evaluating the genetic contribution of monogenic dilated cardiomyopathy

Author

Mazzarotto, Francesco, primary, Tayal, Paz, additional, Buchan, Rachel, additional, Midwinter, William, additional, Wilk, Alicja, additional, Whiffin, Nicola, additional, Govind, Risha, additional, Mazaika, Erica, additional, De Marvao, Antonio, additional, Felkin, Leanne, additional, Dawes, Timothy, additional, Ahmad, Mian, additional, Edwards, Elizabeth, additional, Ing, Alexander, additional, Thomson, Kate, additional, Chan, Laura, additional, Sim, David, additional, Baksi, John, additional, Pantazis, Antonis, additional, Roberts, Angharad, additional, Watkins, Hugh, additional, Funke, Birgit, additional, O’Regan, Declan, additional, Olivotto, Iacopo, additional, Barton, Paul, additional, Prasad, Sanjay, additional, Cook, Stuart, additional, Ware, James, additional, and Walsh, Roddy, additional

Published
2019
Full Text
View/download PDF

49. Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHBand SDHD

Author

Garrett, Alice, Loveday, Chey, King, Laura, Butler, Samantha, Robinson, Rachel, Horton, Carrie, Yussuf, Amal, Choi, Subin, Torr, Beth, Durkie, Miranda, Burghel, George J., Drummond, James, Berry, Ian, Wallace, Andrew, Callaway, Alison, Eccles, Diana, Tischkowitz, Marc, Tatton-Brown, Katrina, Snape, Katie, McVeigh, Terri, Izatt, Louise, Woodward, Emma R., Burnichon, Nelly, Gimenez-Roqueplo, Anne-Paule, Mazzarotto, Francesco, Whiffin, Nicola, Ware, James, Hanson, Helen, Pesaran, Tina, LaDuca, Holly, Buffet, Alexandre, Maher, Eamonn R., and Turnbull, Clare

Abstract

The weight of the evidence to attach to observation of a novel rare missense variant in SDHBor SDHDin individuals with the rare neuroendocrine tumors, pheochromocytomas and paragangliomas (PCC/PGL), is uncertain.

Published
2022
Full Text
View/download PDF

50. Computational prediction of protein subdomain stability in MYBPC3enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation

Author

Thompson, Andrea D., Helms, Adam S., Kannan, Anamika, Yob, Jaime, Lakdawala, Neal K., Wittekind, Samuel G., Pereira, Alexandre C., Jacoby, Daniel L., Colan, Steven D., Ashley, Euan A., Saberi, Sara, Ware, James S., Ingles, Jodie, Semsarian, Christopher, Michels, Michelle, Mazzarotto, Francesco, Olivotto, Iacopo, Ho, Carolyn Y., and Day, Sharlene M.

Abstract

Variants in MYBPC3causing loss of function are the most common cause of hypertrophic cardiomyopathy (HCM). However, a substantial number of patients carry missense variants of uncertain significance (VUS) in MYBPC3. We hypothesize that a structural-based algorithm, STRUM, which estimates the effect of missense variants on protein folding, will identify a subgroup of HCM patients with a MYBPC3VUS associated with increased clinical risk.

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results