Article
Cell Biology
Reiri Sono, Tania M. Larrinaga, Alden Huang, Frank Makhlouf, Xuedong Kang, Jonathan Su, Ryan Lau, Valerie A. Arboleda, Reshma Biniwale, Gregory A. Fishbein, Negar Khanlou, Ming-Sing Si, Gary M. Satou, Nancy Halnon, Glen S. Van Arsdell, Carol C. Gregorio, Stanly Nelson, Marlin Touma
Summary: As a key regulator of thin filament elongation in sarcomere maturation, LMOD2 has been implicated in neonatal dilated cardiomyopathy (DCM) due to thin filament shortening. We present a case of DCM caused by biallelic variants in LMOD2 gene, including the c.1193G>A (p.W398*) nonsense variant. The patient had an unusually late onset of cardiomyopathy during infancy, and histological analysis confirmed the shortening of thin filaments.
Article
Medicine, Research & Experimental
Hong Lian, Shen Song, Wenzheng Chen, Anteng Shi, Haobin Jiang, Shengshou Hu
Summary: This study aimed to characterize the genetic basis of dilated cardiomyopathy (DCM) in heart transplantation (HTx) patients in the Chinese population. The results showed that TTN and FLNC genes harbored a significant number of pathogenic and likely pathogenic variants, and FLNC truncation could lead to severe clinical symptoms in DCM patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Yang Sun, Lei Xiao, Ke Li, Hong Wang, Xiuli Song, Zongzhe Li, Chenze Li, Yanghui Chen, Shiyang Li, Jin Huang, Lun Tan, Dong Hu, Ting Yu, Rui Li, Hong Wang, Li Jin, Leming Shi, Ali J. Marian, Dao Wen Wang
Summary: The study suggests that pathogenic variants and likely pathogenic variants in genes known to cause primary dilated cardiomyopathy are enriched in patients with ischemic dilated cardiomyopathy, indicating that these variants play a role in the susceptibility to cardiac dilatation and dysfunction post myocardial ischemic injury.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Jamie O. Yang, Hapet Shaybekyan, Yan Zhao, Xuedong Kang, Gregory A. Fishbein, Negar Khanlou, Juan C. Alejos, Nancy Halnon, Gary Satou, Reshma Biniwale, Hane Lee, Glen Van Arsdell, Stanley F. Nelson, Marlin Touma
Summary: We present a case study of a 3-year-old female with hypertrophic cardiomyopathy and lactic acidosis. Biopsies of the cardiac and skeletal muscles showed mitochondrial hyperplasia and reduced activity of complex IV. Further analysis through whole exome sequencing revealed compound heterozygous variants in the TSFM gene, which encodes a mitochondrial translation elongation factor. This genetic abnormality led to impaired oxidative phosphorylation and the development of juvenile hypertrophic cardiomyopathy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Genetics & Heredity
Serwa Ghasemi, Mohammad Mahdavi, Majid Maleki, Iman Salahshourifar, Samira Kalayinia
Summary: This study identified a variant in the FBXO32 gene that is associated with recessive DCM. This variant may disrupt the degradation of target proteins in the ubiquitin-proteasome system, leading to DCM.
BMC MEDICAL GENOMICS
(2022)
Article
Cardiac & Cardiovascular Systems
Yu-Xing Liu, Rong Yu, Yue Sheng, Liang-Liang Fan, Yao Deng
Summary: This study reports a Chinese family with cardiomyopathy and sudden cardiac death. Whole-exome sequencing was used to explore the genetic entity of this family, and a novel DES mutation was identified. The study expands the understanding of the relationship between DES mutations and hereditary cardiomyopathy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Genetics & Heredity
Yi-Han Chang, Pei Lin, Jia-Ling Lin, Hsin-Yu Huang, Chao-Kai Hsu, Chih-Hsin Hsu
Summary: Approximately one-third of cases of dilated cardiomyopathy are familial, and a novel desmoplakin mutation was found in two individuals of a Taiwanese family. The patient recovered well after heart transplantation and medical control, while her son underwent different treatment.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Diamanto Skopelitou, Beiping Miao, Aayushi Srivastava, Abhishek Kumar, Magdalena Kuswick, Dagmara Dymerska, Nagarajan Paramasivam, Matthias Schlesner, Jan Lubinski, Kari Hemminki, Asta Forsti, Obul Reddy Bandapalli
Summary: Germline mutations in predisposition genes only contribute to 20% of familial colorectal cancers, with rare potential cancer-predisposing variants remaining poorly explored. A study identified two novel variants in a Polish family, one showing no significant impact on cell proliferation and the other enhancing promoter activity. The findings shed light on unrecognized genetic causes of familial CRC and highlight the importance of 5' UTR variants affecting transcriptional regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Ylenia D'Agostino, Domenico Palumbo, Maria Rosaria Rusciano, Oriana Strianese, Sonia Amabile, Domenico Di Rosa, Elena De Angelis, Valeria Visco, Fabio Russo, Elena Alexandrova, Annamaria Salvati, Giorgio Giurato, Giovanni Nassa, Roberta Tarallo, Gennaro Galasso, Michele Ciccarelli, Alessandro Weisz, Francesca Rizzo
Summary: Dilated cardiomyopathy (DCM) is a complex disease with genetic and environmental factors contributing to its development. Early identification of causative gene mutations is important for genetic diagnosis, pre-symptomatic interventions, and prognosis prediction. Whole-exome sequencing (WES) has emerged as a promising method to identify causal variants in known genes and novel disease-related candidates in DCM.
Article
Cardiac & Cardiovascular Systems
Ting Xie, Yifeng Yang, Ke Gong, Yong Luo, Hui Guo, Ruilin Liu, Lei Wang, Zhiping Tan, Jinwen Luo, Li Xie
Summary: In this study, a novel variant of TNNI3K was identified in ARVC, which not only contributes to the diagnosis of ARVC, but also provides a reference for genetic counseling, and promotes the understanding of the genetic mechanism of cardiomyopathy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Diamanto Skopelitou, Aayushi Srivastava, Beiping Miao, Abhishek Kumar, Dagmara Dymerska, Nagarajan Paramasivam, Matthias Schlesner, Jan Lubinski, Kari Hemminki, Asta Foersti, Obul Reddy Bandapalli
Summary: In this study, two novel variants in the SLC15A4 gene were identified using whole exome sequencing and a familial cancer variant prioritization pipeline, suggesting the involvement of SLC15A4 in the genetic inheritance of familial colorectal cancer for the first time.
MOLECULAR GENETICS AND GENOMICS
(2022)
Article
Biochemistry & Molecular Biology
Cristina Tous, Carmen Munoz-Redondo, Nereida Bravo-Gil, Angela Gavilan, Raquel Maria Fernandez, Juan Antinolo, Elena Navarro-Gonzalez, Guillermo Antinolo, Salud Borrego
Summary: Thyroid carcinoma (TC) can be classified into medullary (MTC) and non-medullary (NMTC). This study aimed to identify susceptibility genes for familial NMTC and non-RET MTC using whole exome sequencing. Rare candidate segregating variants were found in 12 families, with enriched biological processes related to cell proliferation, differentiation, survival, and adhesion. These findings provide insights into molecular mechanisms underlying familial forms of MTC and NMTC, which may contribute to early detection, tailored therapies, and patient management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Daniel J. Schaid, Shannon K. McDonnell, Liesel M. FitzGerald, Lissa DeRycke, Zachary Fogarty, Graham G. Giles, Robert J. MacInnis, Melissa C. Southey, Tu Nguyen-Dumont, Geraldine Cancel-Tassin, Oliver Cussenot, Alice S. Whittemore, Weiva Sieh, Nilah Monnier Ioannidis, Chih-Lin Hsieh, Janet L. Stanford, Johanna Schleutker, Cheryl D. Cropp, John Carpten, Josef Hoegel, Rosalind Eeles, Zsofia Kote-Jarai, Michael J. Ackerman, Christopher J. Klein, Diptasri Mandal, Kathleen A. Cooney, Joan E. Bailey-Wilson, Brian Helfand, William J. Catalona, Fredrick Wiklund, Shaun Riska, Saurabh Bahetti, Melissa C. Larson, Lisa Cannon Albright, Craig Teerlink, Jianfeng Xu, William Isaacs, Elaine A. Ostrander, Stephen N. Thibodeau
Summary: This study uses a two-stage design to identify new genetic variants associated with prostate cancer (PCa) in individuals with a family history of the disease or with a more aggressive form of PCa. The research detected 11 known genes associated with PCa and 10 novel genes, most of which are primarily linked to aggressive PCa risk.
Article
Biochemistry & Molecular Biology
Julia Horjus, Tineke van Mourik-Banda, Marco A. P. Heerings, Marina Hakobjan, Ward De Witte, Dorothea J. Heersema, Anne J. Jansen, Eva M. M. Strijbis, Brigit A. de Jong, Astrid E. J. Slettenaar, Esther M. P. E. Zeinstra, Erwin L. J. Hoogervorst, Barbara Franke, Wiebe Kruijer, Peter J. Jongen, Leo J. Visser, Geert Poelmans
Summary: This study identified 12 rare genetic variants associated with multiple sclerosis through whole exome sequencing and co-segregation analysis, highlighting the involvement of various biological processes related to (de-/re-)myelination and auto-immunity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jeremy E. Schreier, Christa B. Smith, Thomas R. Ioerger, Mary Ann Moran
Summary: Bacteria in phycospheres contribute significantly to the metabolism of ocean primary productivity, but studying the interactions among species in these micron-scale environments is challenging. By culturing a transposon mutant library of copiotrophic bacterium Ruegeria pomeroyi DSS-3 with the diatom Thalassiosira pseu-donana CCMP1335, we identified genes that mediate bacterial interactions in phycosphere communities. These genes had significant effects on R. pomeroyi fitness, indicating explicit cell-cell interactions in the multibacterial phycospheres.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, General & Internal
Cecilia Becattini, Giancarlo Agnelli, Aldo Pietro Maggioni, Francesco Dentali, Andrea Fabbri, Iolanda Enea, Fulvio Pomero, Maria Pia Ruggieri, Andrea Di Lenarda, Michele Gulizia
Summary: The COPE study aims to assess contemporary management strategies and outcomes for patients with acute PE, including in-hospital and 30-day mortality. The results will provide valuable information for clinical practice and improving patient outcomes.
INTERNAL AND EMERGENCY MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Aldostefano Porcari, Chiara Baggio, Enrico Fabris, Marco Merlo, Rossana Bussani, Andrea Perkan, Gianfranco Sinagra
Summary: Endomyocardial biopsy (EMB) is a method for diagnosing various cardiac diseases, and recent advances in imaging techniques provide better non-invasive diagnostic methods, which may require redefining the role of EMB.
HEART FAILURE REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Brisa Pena, Mostafa Adbel-Hafiz, Maria Cavasin, Luisa Mestroni, Orfeo Sbaizero
Summary: Arrhythmogenic cardiomyopathy is an inherited heart muscle disorder characterized by progressive replacement of cardiomyocytes, ventricular dilatation, cardiac dysfunction, arrhythmias, and sudden cardiac death. Molecular biomechanics for these disorders is becoming increasingly important. Atomic force microscopy (AFM) is a well-established technique for studying the mechanobiology of biological samples at the cellular scale. This review discusses the potential of AFM as a tool for assessing the biomechanics involved in arrhythmogenic cardiomyopathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Shanshan Gao, Matthew R. G. Taylor, Luisa Mestroni
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Brisa Pena, Shanshan Gao, Daniele Borin, Giorgia Del Favero, Mostafa Abdel-Hafiz, Nasim Farahzad, Paola Lorenzon, Gianfranco Sinagra, Matthew R. . G. Taylor, Luisa Mestroni, Orfeo Sbaizero
Summary: This study investigated the impact of a mutation associated with Hutchinson-Gilford progeria syndrome on cardiac myocytes. The results showed that the mutation led to changes in beating force and frequency of the myocytes, which were associated with reduced localization of cytoskeletal proteins. These findings contribute to the understanding of the pathology and potential therapeutic approaches for this syndrome.
Article
Cardiac & Cardiovascular Systems
Calum A. MacRae, Matthew R. G. Taylor, Luisa Mestroni, John Moses, Euan A. Ashley, Matthew T. Wheeler, Neal K. Lakdawala, Ray E. Hershberger, Victor Sandor, Michael E. Saunders, Colleen Oliver, Patrice A. Lee, Daniel P. Judge
Summary: This study assessed the effects of ARRY-371797, an oral selective p38 mitogen-activated protein kinase inhibitor, on functional capacity and cardiac function in patients with LMNA-related dilated cardiomyopathy. The results showed that ARRY-371797 was well tolerated and potentially increased functional capacity while lowering the concentration of the cardiac biomarker NT-proBNP.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Dario Catapano, Marco Tontodonato, Saverio D'Elia, Enrica Pezzullo, Francesco Ciaramella, Serena Vettori, Rossana Bussani, Giulio Ciucci, Chiara Collesi, Gianfranco Sinagra, Paolo Golino, Francesco S. S. Loffredo
CIRCULATION-CARDIOVASCULAR IMAGING
(2023)
Article
Cardiac & Cardiovascular Systems
Eva Del Mestre, Carola Pio Loco Detto Gava, Alessia Paldino, Marta Gigli, Maddalena Rossi, Andrea Lalario, Matteo Dal Ferro, Marco Merlo, Gianfranco Sinagra
Summary: DCM is a primary disease of the heart muscle that primarily affects young patients without many other health conditions. It is characterized by structural and/or functional abnormalities leading to systolic dysfunction of the left ventricle or both ventricles, often accompanied by dilation, without a clear underlying cause. Prognostic stratification is important, especially in predicting life-threatening arrhythmic events. A multiparametric approach, including medical history, physical examination, cardiac imaging, and genetic testing, is necessary for accurate diagnosis and risk prediction.
EUROPEAN HEART JOURNAL SUPPLEMENTS
(2023)
Review
Cardiac & Cardiovascular Systems
Alessia Paldino, Maddalena Rossi, Matteo Dal Ferro, Irena Tavcar, Elijah Behr, Sanjay Sharma, Michael Papadakis, Gianfranco Sinagra, Gherardo Finocchiaro
Summary: GEN+PHEN- individuals carry pathogenic genetic variants without phenotypic manifestation of the disease, which poses challenges in clinical management. The variable expressivity of genetic variants within the same family and the unpredictable conversion to overt phenotype complicate decision-making in sports participation. Current guidelines acknowledge the lack of evidence and uncertainties in managing GEN+PHEN- individuals.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2023)
Article
Genetics & Heredity
Stefania Lenarduzzi, Beatrice Spedicati, Beatrice Alessandrini, Paola Tesolin, Alessia Paldino, Marta Gigli, Gianfranco Sinagra, Paolo Gasparini, Matteo Dal Ferro, Giorgia Girotto
Summary: This study focuses on the genetic characterization of hereditary cardiovascular diseases, including cardiomyopathies, channelopathies, and aortopathies and pulmonary arterial hypertension. The majority of patients analyzed in this study were affected by cardiomyopathies, and a higher detection rate was observed in familial forms compared to sporadic cases. Further clinical follow-up and reevaluation of genetic data will be necessary for patients with negative results.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Davide Stolfo, Lars H. Lund, Gianfranco Sinagra, Felix Lindberg, Ulf Dahlstrom, Giuseppe Rosano, Gianluigi Savarese
Summary: This study found that predictors of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers use in heart failure patients include hypertension, younger age, outpatient care, and specialty treatment. The use of these medications was associated with lower risk of cardiovascular mortality/hospitalization and all-cause mortality in a matched cohort. Positive control analysis confirmed these findings, and there were no associations with the negative control outcome.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
(2023)
Article
Cardiac & Cardiovascular Systems
Vincenzo Nuzzi, Aldostefano Porcari, Marta Gigli, Francesco Zaja, Franca Dore, Rossana Bussani, Gianfranco Sinagra, Marco Merlo
Summary: This case report describes a 57-year-old asymptomatic man with incidental findings of myocardial necrosis and left ventricular wall thickening. Further investigations revealed monoclonal gammopathy and high levels of lambda free light chains, leading to the diagnosis of isolated cardiac AL amyloidosis. The study emphasizes the importance of an accurate diagnostic flowchart and tailored management for this condition.
EUROPEAN HEART JOURNAL-CASE REPORTS
(2023)
Article
Cardiac & Cardiovascular Systems
Elisabetta Salvioni, Alice Bonomi, Damiano Magri, Marco Merlo, Beatrice Pezzuto, Mattia Chiesa, Massimo Mapelli, Nikita Baracchini, Gianfranco Sinagra, Massimo Piepoli, Piergiuseppe Agostoni
Summary: Cardiopulmonary exercise tests (CPET) are crucial for evaluating the functional capacity of chronic heart failure (HF) patients. The MECKI score, developed by a group of Italian centers skilled in HF management and CPET analysis, has been extensively validated and shown to be effective in risk stratification for HF. The MECKI score research group has grown over time and is now investigating other areas such as cardiomyopathy.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2023)
Letter
Cardiac & Cardiovascular Systems
Alberto Guarnaccia, Gianfranco Sinagra, John G. F. Cleland
Review
Cardiac & Cardiovascular Systems
Sindhu Chadalawada, Anis Rassi Jr, Omar Samara, Anthony Monzon, Deepika Gudapati, Lilian Vargas Barahona, Peter Hyson, Stefan Sillau, Luisa Mestroni, Matthew Taylor, Maria Da Consolacao Vieira Moreira, Kristen DeSanto, Nelson I. Agudelo Higuita, Carlos Franco-Paredes, Andres F. Henao-Martinez
Summary: The study found that the annual mortality risk in chronic Chagas cardiomyopathy is significant, with cardiovascular causes being the main contributor. Patients with low left ventricular ejection fraction and those classified as AHA stages C and C/D have an increased mortality risk.