TTN truncation variants produce sarcomere-integrating proteins of uncertain functional significance
Titin (TTN) is one of the largest and most complex proteins expressed in humans, and truncation variants are the most prevalent genetic lesion identified in individuals with dilated cardiomyopathy (DCM) or other disorders of impaired cardiac contractility. Two reports in this issue of the JCI shed light on a potential mechanism involving truncated TTN sarcomere integration and the potential for disruption of sarcomere structural integrity. Kellermayer, Tordai, and colleagues confirmed the presence of truncated TTN protein in human DCM samples. McAfee and authors developed a patient-specific TTN antibody to study truncated ...
Source: Journal of Clinical Investigation - January 16, 2024 Category: Biomedical Science Authors: J. Travis Hinson, Stuart G. Campbell Source Type: research
Truncated titin protein in dilated cardiomyopathy incorporates into the sarcomere and transmits force
(Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - January 16, 2024 Category: Biomedical Science Authors: Quentin McAfee, Matthew A. Caporizzo, Keita Uchida, Kenneth C. Bedi Jr., Kenneth B. Margulies, Zolt Arany, Benjamin L. Prosser Source Type: research
A Novel < em > TPM1 < /em > Mutation Causes Familial Hypertrophic Cardiomyopathy in an Indian Family: Genetic and Clinical Correlation
We present a case of a novel heterozygous TPM1 mutation, NM_001018005.2:c.203A>G, p.Gln68Arg; co-segregating in an Indian family with hypertrophic cardiomyopathy. Our report expands the mutational spectrum of HCM due to TPM1 and provides the correlated cardiac phenotype.PMID:38223010 | PMC:PMC10784234 | DOI:10.1007/s12291-022-01036-w (Source: Clinical Biochemistry)
Source: Clinical Biochemistry - January 15, 2024 Category: Biochemistry Authors: Prabodh Kumar Ganesh Paramasivam Tom Devasia Mukund Prabhu Maneesh K Rai K Prakashini Sandeep Mallya Dinesh Reghunathan A Megha Krishnananda Nayak Rajasekhar Moka Source Type: research
DMD deletions underlining mild dystrophinopathies: literature review highlights phenotype-related mutation clusters and provides insights about genetic mechanisms and prognosis
DMD gene pathogenic variations cause a spectrum of phenotypes, ranging from severe Duchenne muscular dystrophy, the Becker milder cases, the intermediate or very mild muscle phenotypes invariably characterized by high CK, and the ultrarare fully-asymptomatic cases. Besides these phenotypes, X-linked dilated cardiomyopathy is also caused by DMD mutations. Males carrying DMD deletions with absent or very mild phenotypes have been sparsely described. We performed a horizon scan on public datasets to enroll males with the above phenotypes and carrying DMD deletions to delineate myopathic genotype-phenotype relationships. We in...
Source: Frontiers in Neurology - January 15, 2024 Category: Neurology Source Type: research
Downregulation of Wtap causes dilated cardiomyopathy and heart failure
In this study, we identified Wilms' tumor 1-associating protein (WTAP, a key regulatory protein of the m6A RNA methyltransferase complex) as a key regulator of heart function and cardiac diseases. WTAP is associated with heart development, and its expression is downregulated in both human and mice with heart failure. Cardiomyocyte-specific knockout of Wtap (Wtap-CKO) induces dilated cardiomyopathy, heart failure and neonatal death. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - January 13, 2024 Category: Cytology Authors: Lei Shi, Xinzhi Li, Meiwei Zhang, Cong Qin, Zhiguo Zhang, Zheng Chen Source Type: research
CRYAB stop-loss variant causes rare syndromic dilated cardiomyopathy with congenital cataract: expanding the phenotypic and mutational spectrum of alpha-B crystallinopathy
This study expands the mutational spectrum ofCRYAB and deepens our understanding of the complex phenotypes of alpha-B crystallinopathies. (Source: Journal of Human Genetics)
Source: Journal of Human Genetics - January 12, 2024 Category: Genetics & Stem Cells Source Type: research
Network-based identification of diagnosis-specific trans-omic biomarkers via integration of multiple omics data
Biosystems. 2024 Feb;236:105122. doi: 10.1016/j.biosystems.2024.105122. Epub 2024 Jan 8.ABSTRACTThe integration of multiple omics data promises to reveal new insights into the pathogenic mechanisms of complex human diseases, with the potential to identify avenues for the development of targeted therapies for disease subtypes. However, the extraction of diagnostic/disease-specific biomarkers from multiple omics data with biological pathway knowledge is a challenging issue in precision medicine. In this paper, we present a novel computational method to identify diagnosis-specific trans-omic biomarkers from multiple omics dat...
Source: Biosystems - January 10, 2024 Category: Biotechnology Authors: Md Mamunur Rashid Momoko Hamano Midori Iida Michio Iwata Toshiyuki Ko Seitaro Nomura Issei Komuro Yoshihiro Yamanishi Source Type: research
Navigating the Complex Landscape of Atrial Functional Mitral Regurgitation: Insights, Challenges, and Emerging Interventions
Functional or secondary mitral valve regurgitation occurs as a consequence of abnormalities in left-sided cardiac geometry and function, in the setting of structurally normal mitral valve leaflets and chordal apparatus. It is frequently associated with left ventricular enlargement or regional dysfunction causing mitral leaflet tethering and annular dilatation, as seen in dilated cardiomyopathy or ischemic heart disease. Atrial functional mitral regurgitation (AFMR) has sparked increasing interest in recent years and is characterized by left atrial and mitral annular dilatation despite normal left ventricular size and systo...
Source: The American Journal of Cardiology - January 10, 2024 Category: Cardiology Authors: Sushil Allen Luis, Hector I. Michelena, Vuyisile T. Nkomo Tags: Editorial Source Type: research
Severity of Left Ventricular Dysfunction in Patients With Tachycardia-Induced Cardiomyopathy: Impacts on Remodeling After Atrial Flutter Ablation
Tachycardia-induced cardiomyopathy (TIC) is a unique cause of nonischemic dilated cardiomyopathy, defined as reversible left ventricular (LV) systolic dysfunction resulting from a sustained fast heart rate.1 It has been reported in patients with incessant or very frequent tachyarrhythmias with an incidence ranging from 3% to 50%, depending on the arrhythmia type and population.2 –6 Although atrial fibrillation is the most common and most studied tachyarrhythmia associated with arrhythmia-induced cardiomyopathy, atrial flutter is also a common etiology. (Source: The American Journal of Cardiology)
Source: The American Journal of Cardiology - January 10, 2024 Category: Cardiology Authors: Hugo De Larochelli ère, François Brouillette, Patrick Lévesque, Nicolas Dognin, Raphaël St-Germain, Goran Rimac, Sylvain Lemay, François Philippon, Mario Sénéchal Source Type: research
Characterization of cardiac involvement in patients with LMNA splice-site mutation –related dilated cardiomyopathy and sudden cardiac death
Discussion: Above all, Cardiaccardiac involvement in patients with LMNA splice-site mutation presented with a high rate of SCD. Implanting a pacemaker significantly reduced the SCD rate in non-DCM patients with AVB. The pathogenic characterization was not only haveinvolved suppressed the expression of the healthy LMNA allele, but was also associated with abnormal expression and distribution of desmin and Cx43. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - January 8, 2024 Category: Genetics & Stem Cells Source Type: research
The outcomes of a standardized protocol for extracorporeal mechanical circulatory support selection-left ventricular challenge protocol
AbstractThere are no criteria for surgical mechanical circulatory system (MCS) selection for acute heart failure. Since 2021, we have utilized cardiopulmonary bypass system to assess patients ’ heart and lung condition to inform surgical MCS selection. we aimed to retrospectively analyze the outcomes of treatments administered using our protocol. We analyzed the data of 19 patients who underwent surgical MCS implantation. We compared patients’ characteristics across the biventricular -assist device (BiVAD), central Y-Y extracorporeal membrane oxygenation (ECMO), central ECMO, and left VAD (LVAD) systems. Patients' diag...
Source: Journal of Artificial Organs - January 8, 2024 Category: Transplant Surgery Source Type: research
Generation of CRISPR-Cas9 edited human induced pluripotent stem cell line carrying BAG3 V468M mutation in its BAG domain
Stem Cell Res. 2023 Dec 21;74:103294. doi: 10.1016/j.scr.2023.103294. Online ahead of print.ABSTRACTBCL2-Associated Athanogene 3 (BAG3) gene was identified mutated in patients with dilated cardiomyopathy (DCM), an important cause of heart failure and premature death. BAG3 is a cytoprotective co-chaperonne protein involved in many cellular process with a central role in the maintenance of protostasis. We generated two human induced pluripotent stem cell lines (hiPSc), one carrying the heterozygous, the other the homozygous p.V468M mutation identified in DCM familial cases. All lines expressed pluripotent markers, had normal...
Source: Cell Research - January 6, 2024 Category: Cytology Authors: Laetitia Duboscq-Bidot B énédicte Hoareau Flavie Ader Vincent Fontaine Eric Villard Source Type: research
Circulating biomarker- and magnetic resonance-based nomogram predicting long-term outcomes in dilated cardiomyopathy
CONCLUSIONS: We established and validated a circulating biomarker- and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients, which might help risk stratification and decision-making in clinical practice.PMID:38178323 | DOI:10.1097/CM9.0000000000002688 (Source: Chinese Medical Journal)
Source: Chinese Medical Journal - January 5, 2024 Category: General Medicine Authors: Yupeng Liu Wenyao Wang Jingjing Song Jiancheng Wang Yi Fu Yida Tang Source Type: research
Circulating biomarker- and magnetic resonance-based nomogram predicting long-term outcomes in dilated cardiomyopathy
CONCLUSIONS: We established and validated a circulating biomarker- and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients, which might help risk stratification and decision-making in clinical practice.PMID:38178323 | DOI:10.1097/CM9.0000000000002688 (Source: Chinese Medical Journal)
Source: Chinese Medical Journal - January 5, 2024 Category: General Medicine Authors: Yupeng Liu Wenyao Wang Jingjing Song Jiancheng Wang Yi Fu Yida Tang Source Type: research
