12 results on '"Heliö, Tiina"'
Search Results
2. GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy
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Heliö, Krista, Mäyränpää, Mikko I., Saarinen, Inka, Ahonen, Saija, Junnila, Heidi, Tommiska, Johanna, Weckström, Sini, Holmström, Miia, Toivonen, Mia, Nikus, Kjell, Hathaway, Julie, Siivonen, Pauli, Muona, Mikko, Sistonen, Johanna, Salmenperä, Pertteli, Gentile, Massimiliano, Paananen, Jussi, Myllykangas, Samuel, Alastalo, Tero-Pekka, Heliö, Tiina, Koskenvuo, Juha, Faculty of Medicine, HUSLAB, Department of Pathology, HUS Heart and Lung Center, HUS Medical Imaging Center, Department of Diagnostics and Therapeutics, Clinicum, Department of Medicine, Tampere University, Clinical Medicine, and TAYS Heart Centre
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MYZAP ,GENETICS ,RECEPTOR ,1184 Genetics, developmental biology, physiology ,PROTEIN ,MYOZAP ,autosomal recessive ,ORGANIZATION ,GUIDELINES ,dilated cardiomyopathy ,Molecular Medicine ,GCOM1 ,3111 Biomedicine ,cardiomyopathy ,Genetics (clinical) ,FORM ,Original Research - Abstract
Background: Familial dilated cardiomyopathy (DCM) is a monogenic disorder typically inherited in an autosomal dominant pattern. We have identified two Finnish families with familial cardiomyopathy that is not explained by a variant in any previously known cardiomyopathy gene. We describe the cardiac phenotype related to homozygous truncating GCOM1 variants. Methods and Results: This study included two probands and their relatives. All the participants are of Finnish ethnicity. Whole-exome sequencing was used to test the probands; bi-directional Sanger sequencing was used to identify the GCOM1 variants in probands’ family members. Clinical evaluation was performed, medical records and death certificates were obtained. Immunohistochemical analysis of myocardial samples was conducted. A homozygous GCOM1 variant was identified altogether in six individuals, all considered to be affected. None of the nine heterozygous family members fulfilled any cardiomyopathy criteria. Heart failure was the leading clinical feature, and the patients may have had a tendency for atrial arrhythmias. Conclusions: This study demonstrates the significance of GCOM1 variants as a cause of human cardiomyopathy and highlights the importance of searching for new candidate genes when targeted gene panels do not yield a positive outcome. publishedVersion
- Published
- 2021
3. Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations.
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Le Dour, Caroline, Chatzifrangkeskou, Maria, Macquart, Coline, Magiera, Maria M., Peccate, Cécile, Jouve, Charlène, Virtanen, Laura, Heliö, Tiina, Aalto-Setälä, Katriina, Crasto, Silvia, Cadot, Bruno, Cardoso, Déborah, Mougenot, Nathalie, Adesse, Daniel, Di Pasquale, Elisa, Hulot, Jean-Sébastien, Taimen, Pekka, Janke, Carsten, and Muchir, Antoine
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DILATED cardiomyopathy ,SERUM response factor ,TUBULINS ,CONNEXIN 43 ,CYTOSKELETON ,TRANSCRIPTION factors ,MICROTUBULES - Abstract
Mutations in the lamin A/C gene (LMNA) cause dilated cardiomyopathy associated with increased activity of ERK1/2 in the heart. We recently showed that ERK1/2 phosphorylates cofilin-1 on threonine 25 (phospho(T25)-cofilin-1) that in turn disassembles the actin cytoskeleton. Here, we show that in muscle cells carrying a cardiomyopathy-causing LMNA mutation, phospho(T25)-cofilin-1 binds to myocardin-related transcription factor A (MRTF-A) in the cytoplasm, thus preventing the stimulation of serum response factor (SRF) in the nucleus. Inhibiting the MRTF-A/SRF axis leads to decreased α-tubulin acetylation by reducing the expression of ATAT1 gene encoding α-tubulin acetyltransferase 1. Hence, tubulin acetylation is decreased in cardiomyocytes derived from male patients with LMNA mutations and in heart and isolated cardiomyocytes from Lmna
p.H222P/H222P male mice. In Atat1 knockout mice, deficient for acetylated α-tubulin, we observe left ventricular dilation and mislocalization of Connexin 43 (Cx43) in heart. Increasing α-tubulin acetylation levels in Lmnap.H222P/H222P mice with tubastatin A treatment restores the proper localization of Cx43 and improves cardiac function. In summary, we show for the first time an actin-microtubule cytoskeletal interplay mediated by cofilin-1 and MRTF-A/SRF, promoting the dilated cardiomyopathy caused by LMNA mutations. Our findings suggest that modulating α-tubulin acetylation levels is a feasible strategy for improving cardiac function. Lamin A/C gene mutations cause dilated cardiomyopathy associated with cofilin-1 phosphorylation and actin destabilization. Here, the authors show that phosphorylated cofilin-1 blunts the MRTF-A/SRF axis, leading to decreased tubulin acetylation and altered cardiac structure and function. [ABSTRACT FROM AUTHOR]- Published
- 2022
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4. A novel mutation, Arg71Thr, in the δ-sarcoglycan gene is associated with dilated cardiomyopathy
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Kärkkäinen, Satu, Miettinen, Raija, Tuomainen, Petri, Kärkkäinen, Päivi, Heliö, Tiina, Reissell, Eeva, Kaartinen, Maija, Toivonen, Lauri, Nieminen, Markku S., Kuusisto, Johanna, Laakso, Markku, and Peuhkurinen, Keijo
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- 2003
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5. The Cardiomyopathy Registry of the EURObservational Research Programme of the European Society of Cardiology: baseline data and contemporary management of adult patients with cardiomyopathies
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Charron, Philippe, Elliott, Perry M, Gimeno, Juan R, Caforio, Alida L P, Kaski, Juan Pablo, Tavazzi, Luigi, Tendera, Michal, Maupain, Carole, Laroche, Cécile, Rubis, Pawel, Jurcut, Ruxandra, Calò, Leonardo, Heliö, Tiina M, Sinagra, Gianfranco, Zdravkovic, Marija, Kavoliūnienė, Aušra, Felix, Stephan B, Grzybowski, Jacek, Losi, Maria-Angela, Asselbergs, Folkert W, García-Pinilla, José Manuel, Salazar-Mendiguchia, Joel, Mizia-Stec, Katarzyna, Maggioni, Aldo P, Anastasakis, Aris, Biagini, Elena, Bilinska, Zofia, Castro, Francisco Jose, Celutkiene, Jelena, Chakova, Natalija, Chmielewski, Przemyslaw, Drago, Fabrizio, Frigy, Attila, Frustaci, Andrea, Garcia-Pavia, Pablo, Hinic, Sasa, Kindermann, Ingrid, Limongelli, Giuseppe, Medrano, Constancio, Monserrat, Lorenzo, Olusegun-Joseph, Akinsanya, Ripoll-Vera, Tomas, Rocha Lopes, Luis, Saad, Aly, Sala, Simone, Seferovic, Petar M, Sepp, Robert, Urbano-Moral, Jose Angel, Villacorta, Eduardo, Wybraniec, Maciej, Yotti, Raquel, Zachara, Elisabetta, Zorio, Esther, Charron, P., Elliott, P. M., Gimeno, J. R., Caforio, A. L. P., Kaski, J. P., Tavazzi, L., Tendera, M., Maupain, C., Laroche, C., Rubis, P., Jurcut, R., Calo, L., Helio, T. M., Sinagra, G., Zdravkovic, M., Kavoliuniene, A., Felix, S. B., Grzybowski, J., Losi, M. A., Asselbergs, F. W., Garcia-Pinilla, J. M., Salazar-Mendiguchia, J., Mizia-Stec, K., Maggioni, A. P., Anastasakis, A., Biagini, E., Bilinska, Z., Castro, F. J., Celutkiene, J., Chakova, N., Chmielewski, P., Drago, F., Frigy, A., Frustaci, A., Garcia-Pavia, P., Hinic, S., Kindermann, I., Limongelli, G., Medrano, C., Monserrat, L., Olusegun-Joseph, A., Ripoll-Vera, T., Lopes, L. R., Saad, A., Sala, S., Seferovic, P. M., Sepp, R., Urbano-Moral, J. A., Villacorta, E., Wybraniec, M., Yotti, R., Zachara, E., Zorio, E., Charron, Philippe, Elliott, Perry M., Gimeno, Juan R., Caforio, Alida L. P., Kaski, Juan Pablo, Tavazzi, Luigi, Tendera, Michal, Maupain, Carole, Laroche, Cécile, Rubis, Pawel, Jurcut, Ruxandra, Calò, Leonardo, Heliö, Tiina M., Sinagra, Gianfranco, Zdravkovic, Marija, Kavoliuniene, Aušra, Felix, Stephan B., Grzybowski, Jacek, Losi, Maria-Angela, Asselbergs, Folkert W., García-Pinilla, José Manuel, Salazar-Mendiguchia, Joel, Mizia-Stec, Katarzyna, Maggioni, Aldo P., Anastasakis, Ari, Biagini, Elena, Bilinska, Zofia, Castro, Francisco Jose, Celutkiene, Jelena, Chakova, Natalija, Chmielewski, Przemyslaw, Drago, Fabrizio, Frigy, Attila, Frustaci, Andrea, Garcia-Pavia, Pablo, Hinic, Sasa, Kindermann, Ingrid, Limongelli, Giuseppe, Medrano, Constancio, Monserrat, Lorenzo, Olusegun-Joseph, Akinsanya, Ripoll-Vera, Toma, Lopes, Luis Rocha, Saad, Aly, Sala, Simone, Seferovic, Petar M., Sepp, Robert, Urbano-Moral, Jose Angel, Villacorta, Eduardo, Wybraniec, Maciej, Yotti, Raquel, Zachara, Elisabetta, Zorio, Esther, Charron, P, Elliott, Pm, Gimeno, Jr, Caforio, Alp, Kaski, Jp, Tavazzi, L, Tendera, M, Maupain, C, Laroche, C, Rubis, P, Jurcut, R, Calò, L, Heliö, Tm, Sinagra, G, Zdravkovic, M, Kavoliuniene, A, Felix, Sb, Grzybowski, J, Losi, Ma, Asselbergs, Fw, García-Pinilla, Jm, Salazar-Mendiguchia, J, Mizia-Stec, K, and Maggioni, Ap
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Male ,Cardiomyopathy ,030204 cardiovascular system & hematology ,Defibrillator ,0302 clinical medicine ,Dilated ,Age Factor ,030212 general & internal medicine ,Prospective Studies ,Registries ,Prospective cohort study ,Arrhythmogenic Right Ventricular Dysplasia ,Cardiomyopathy, Restrictive ,adult ,Hypertrophic cardiomyopathy ,Age Factors ,Disease Management ,Dilated cardiomyopathy ,Middle Aged ,Magnetic Resonance Imaging ,3. Good health ,Arrhythmogenic right ventricular dysplasia ,Europe ,Arrhythmogenic right ventricular ,Female ,Cardiology and Cardiovascular Medicine ,Cardiomyopathies ,Human ,Adult ,Cardiomyopathy, Dilated ,Registry ,medicine.medical_specialty ,Cardiomyopathies, adult ,Restrictive ,Context (language use) ,Right ventricular cardiomyopathy ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Cardiomyopathie ,business.industry ,Restrictive cardiomyopathy ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Prospective Studie ,Hypertrophic ,business ,Defibrillators - Abstract
Aims The Cardiomyopathy Registry of the EURObservational Research Programme is a prospective, observational, and multinational registry of consecutive patients with four cardiomyopathy subtypes: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). We report the baseline characteristics and management of adults enrolled in the registry. ................................................................................................................................................................................................... Methods and results A total of 3208 patients were enrolled by 69 centres in 18 countries [HCM (n = 1739); DCM (n = 1260); ARVC (n = 143); and RCM (n = 66)]. Differences between cardiomyopathy subtypes (P < 0.001) were observed for age at diagnosis, history of familial disease, history of sustained ventricular arrhythmia, use of magnetic resonance imaging or genetic testing, and implantation of defibrillators. When compared with probands, relatives had a lower age at diagnosis (P < 0.001), but a similar rate of symptoms and defibrillators. When compared with the Long-Term phase, patients of the Pilot phase (enrolled in more expert centres) had a more frequent rate of familial disease (P < 0.001), were more frequently diagnosed with a rare underlying disease (P < 0.001), and more frequently implanted with a defibrillator (P = 0.023). Comparing four geographical areas, patients from Southern Europe had a familial disease more frequently (P < 0.001), were more frequently diagnosed in the context of a family screening (P < 0.001), and more frequently diagnosed with a rare underlying disease (P < 0.001). ................................................................................................................................................................................................... Conclusion By providing contemporary observational data on characteristics and management of patients with cardiomyopathies, the registry provides a platform for the evaluation of guideline implementation. Potential gaps with existing recommendations are discussed as well as some suggestions for improvement of health care provision in Europe.
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- 2018
6. Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry.
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Asselbergs, Folkert W., Sammani, Arjan, Elliott, Perry, Gimeno, Juan R., Tavazzi, Luigi, Tendera, Michael, Kaski, Juan Pablo, Maggioni, Aldo P., Rubis, Pawel P., Jurcut, Ruxandra, Heliö, Tiina, Calò, Leonardo, Sinagra, Gianfranco, Zdravkovic, Marija, Olivotto, Iacopo, Kavoliūnienė, Aušra, Laroche, Cécile, Caforio, Alida L.P., and Charron, Philippe
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DILATED cardiomyopathy ,CARDIOVASCULAR diseases risk factors ,PHENOTYPES - Abstract
Aims: Dilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non‐familial (sporadic) DCM (SDCM) across Europe. Methods and results: Patients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P < 0.01), had less severe disease phenotype at presentation (P < 0.02), more favourable baseline cardiovascular risk profiles (P ≤ 0.007), and less medication use (P ≤ 0.042). Outcome at 1 year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25–0.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02–1.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P < 0.01) and had higher genetic yield (55% vs. 22%, P < 0.01). Conclusions: We observed that FDCM and SDCM have significant differences at baseline but similar short‐term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non‐marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Deleterious assembly of the lamin A/C mutant p.S143P causes ER stress in familial dilated cardiomyopathy.
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West, Gun, Gullmets, Josef, Virtanen, Laura, Song-Ping Li, Keinänen, Anni, Shimi, Takeshi, Mauermann, Monika, Heliö, Tiina, Kaartinen, Maija, Ollila, Laura, Kuusisto, Johanna, Eriksson, John E., Goldman, Robert D., Herrmann, Harald, and Taimen, Pekka
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CARDIOMYOPATHIES ,DILATED cardiomyopathy ,IDIOPATHIC dilated cardiomyopathy ,HYPERTROPHIC cardiomyopathy ,MYOCARDITIS - Abstract
Mutation of the LMNA gene, encoding nuclear lamin A and lamin C (hereafter lamin A/C), is a common cause of familial dilated cardiomyopathy (DCM). Among Finnish DCM patients, the founder mutation c.427T>C (p.S143P) is the most frequently reported genetic variant. Here, we show that p.S143P lamin A/C is more nucleoplasmic and soluble than wild-type lamin A/C and accumulates into large intranuclear aggregates in a fraction of cultured patient fibroblasts as well as in cells ectopically expressing either FLAG- or GFP-tagged p.S143P lamin A. In fluorescence loss in photobleaching (FLIP) experiments, non-aggregated EGFP-tagged p.S143P lamin A was significantly more dynamic. In in vitro association studies, p.S143P lamin A failed to form appropriate filament structures but instead assembled into disorganized aggregates similar to those observed in patient cell nuclei. A whole-genome expression analysis revealed an elevated unfolded protein response (UPR) in cells expressing p.S143P lamin A/C. Additional endoplasmic reticulum (ER) stress induced by tunicamycin reduced the viability of cells expressing mutant lamin further. In summary, p.S143P lamin A/C affects normal lamina structure and influences the cellular stress response, homeostasis and viability. [ABSTRACT FROM AUTHOR]
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- 2016
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8. Genetics and genotype-phenotype correlations in Finnish patients with dilated cardiomyopathy.
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Akinrinade, Oyediran, Ollila, Laura, Vattulainen, Sanna, Tallila, Jonna, Gentile, Massimiliano, Salmenperä, Pertteli, Koillinen, Hannele, Kaartinen, Maija, Nieminen, Markku S., Myllykangas, Samuel, Alastalo, Tero-Pekka, Koskenvuo, Juha W., and Heliö, Tiina
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Aims Despite our increased understanding of the genetic basis of dilated cardiomyopathy (DCM), the clinical utility and yield of clinically meaningful findings of comprehensive next-generation sequencing (NGS)-based genetic diagnostics in DCM has been poorly described. We utilized a high-quality oligonucleotide-selective sequencing (OS-Seq)-based targeted sequencing panel to investigate the genetic landscape of DCM in Finnish population and to evaluate the utility of OS-Seq technology as a novel comprehensive diagnostic tool. Methods and results Using OS-Seq, we targeted and sequenced the coding regions and splice junctions of 101 genes associated with cardiomyopathies in 145 unrelated Finnish patients with DCM. We developed effective bioinformatic variant filtering strategy and implemented strict variant classification scheme to reveal diagnostic yield and genotype-phenotype correlations. Implemented OS-Seq technology provided high coverage of the target region (median coverage 410× and 99.42% of the nucleotides were sequenced at least 15× read depth). Diagnostic yield was 35.2% (familial 47.6% and sporadic 25.6%, P = 0.004) when both pathogenic and likely pathogenic variants are considered as disease causing. Of these, 20 (53%) were titin (TTN) truncations (non-sense and frameshift) affecting all TTN transcripts. TTN truncations accounted for 20.6% and 14.6% of the familial and sporadic DCM cases, respectively. Conclusion Panel-based, high-quality NGS enables high diagnostic yield especially in the familial form of DCM, and bioinformatic variant filtering is a reliable step in the process of interpretation of genomic data in a clinical setting. [ABSTRACT FROM AUTHOR]
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- 2015
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9. Lamin A/C mutation affecting primarily the right side of the heart.
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Ollila, Laura, Kuusisto, Johanna, Peuhkurinen, Keijo, Kärkkäinen, Satu, Tuomainen, Petri, Kaartinen, Maija, Raheem, Olayinka, Udd, Bjarne, Magga, Jarkko, Rapola, Janne, Lahtinen, Annukka M., Lehtonen, Eero, Holmström, Miia, Kivistö, Sari, Widén, Elisabeth, Saksa, Markku, and Heliö, Tiina
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DILATED cardiomyopathy ,RIGHT heart ventricle diseases ,TRICUSPID valve insufficiency ,PHENOTYPES ,ELECTRON microscopy ,CARDIOMYOPATHIES ,CARDIAC patients - Abstract
LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC) is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We screened 135 unrelated cardiomyopathy patients for LMNA mutations. Because of unusual phenotype, two patients were screened for the known Finnish ARVC-related mutations of desmosomal genes, and their Plakophilin-2b gene was sequenced. Myocardial samples from two patients were examined by immunohistochemical plakoglobin staining and in one case by electron microscopy. We found a new LMNA mutation Phe237Ser in a family of five affected members with a cardiomyopathy affecting primarily the right side of the heart. The phenotype resembles ARVC but does not fulfill the Task Force Criteria. The main clinical manifestations of the mutation were severe tricuspid insufficiency, right ventricular enlargement and failure. Three of the affected patients died of the heart disease, and the two living patients received heart transplants at ages 44 and 47. Electron microscopy showed nuclear blebbing compatible with laminopathy. Immunohistochemical analysis did not suggest desmosomal pathology. No desmosomal mutations were found. The Phe237Ser LMNA mutation causes a phenotype different from traditional cardiolaminopathy. Our findings suggest that cardiomyopathy affecting primarily the right side of the heart is not always caused by desmosomal pathology. Our observations highlight the challenges in classifying cardiomyopathies, as there often is significant overlap between the traditional categories. [ABSTRACT FROM AUTHOR]
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- 2013
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10. A novel mutation, Ser143Pro, in the lamin A/C gene is common in finnish patients with familial dilated cardiomyopathy.
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Kärkkäinen, Satu, Heliö, Tiina, Miettinen, Raija, Tuomainen, Petri, Peltola, Paula, Rummukainen, Juha, Ylitalo, Kari, Kaartinen, Maija, Kuusisto, Johanna, Toivonen, Lauri, Nieminen, Markku S, Laakso, Markku, and Peuhkurinen, Keijo
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Aims The mutations most frequently associated with dilated cardiomyopathy (DCM) have been reported in the lamin A/C gene. The role of variants of the lamin A/C gene was investigated in patients with DCM from eastern and southern Finland. [ABSTRACT FROM PUBLISHER]
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- 2004
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11. Publisher Correction: Relevance of Titin Missense and Non-Frameshifting Insertions/Deletions Variants in Dilated Cardiomyopathy.
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Akinrinade, Oyediran, Heliö, Tiina, Lekanne Deprez, Ronald H., Jongbloed, Jan D. H., Boven, Ludolf G., van den Berg, Maarten P., Pinto, Yigal M., Alastalo, Tero-Pekka, Myllykangas, Samuel, van Spaendonck-Zwarts, Karin, van Tintelen, J. Peter, van der Zwaag, Paul A., and Koskenvuo, Juha
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CONNECTIN , *MISSENSE mutation , *DILATED cardiomyopathy - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
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- 2020
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12. Modeling of LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells.
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Shah, Disheet, Virtanen, Laura, Prajapati, Chandra, Kiamehr, Mostafa, Gullmets, Josef, West, Gun, Kreutzer, Joose, Pekkanen-Mattila, Mari, Heliö, Tiina, Kallio, Pasi, Taimen, Pekka, and Aalto-Setälä, Katriina
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PLURIPOTENT stem cells ,INDUCED pluripotent stem cells ,DILATED cardiomyopathy ,CELL anatomy ,HEART failure ,THERAPEUTICS - Abstract
Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure and heart transplantation. A portion of familial DCM is due to mutations in the LMNA gene encoding the nuclear lamina proteins lamin A and C and without adequate treatment these patients have a poor prognosis. To get better insights into pathobiology behind this disease, we focused on modeling LMNA-related DCM using human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM). Primary skin fibroblasts from DCM patients carrying the most prevalent Finnish founder mutation (p.S143P) in LMNA were reprogrammed into hiPSCs and further differentiated into cardiomyocytes (CMs). The cellular structure, functionality as well as gene and protein expression were assessed in detail. While mutant hiPSC-CMs presented virtually normal sarcomere structure under normoxia, dramatic sarcomere damage and an increased sensitivity to cellular stress was observed after hypoxia. A detailed electrophysiological evaluation revealed bradyarrhythmia and increased occurrence of arrhythmias in mutant hiPSC-CMs on β-adrenergic stimulation. Mutant hiPSC-CMs also showed increased sensitivity to hypoxia on microelectrode array and altered Ca
2+ dynamics. Taken together, p.S143P hiPSC-CM model mimics hallmarks of LMNA-related DCM and provides a useful tool to study the underlying cellular mechanisms of accelerated cardiac degeneration in this disease. [ABSTRACT FROM AUTHOR]- Published
- 2019
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