Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy
| Autor: | Maarten P. van den Berg, Anna Posafalvi, Denise Hilfiker-Kleiner, Richard J. Sinke, Rowida Almomani, J. Peter van Tintelen, Marielle Alders, Jolanda van der Velden, Karen Sliwa, Peter van der Meer, Jan D. H. Jongbloed, Karin Y. van Spaendonck-Zwarts, Ilse A. E. Bollen, Dirk J. van Veldhuisen, Irene M. van Langen |
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| Přispěvatelé: | Ethical, Legal, Social Issues in Genetics (ELSI), Reproductive Origins of Adult Health and Disease (ROAHD), Cardiovascular Centre (CVC), Health Psychology Research (HPR), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Physiology, ICaR - Heartfailure and pulmonary arterial hypertension, Human Genetics, ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Other Research |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Cardiomyopathy Dilated STAT3 Transcription Factor PROGNOSIS Peripartum cardiomyopathy Cardiomyopathy Titin POSTPARTUM CARDIOMYOPATHY medicine.disease_cause EJECTION FRACTION Cohort Studies Young Adult Genetics MANAGEMENT Humans Medicine Connectin Clinical significance PREDICTORS Mutation biology business.industry Dilated cardiomyopathy STIFFNESS Puerperal Disorders medicine.disease DYSFUNCTION Pedigree PREGNANCY Heart failure biology.protein HEART-FAILURE Female MYH7 BROMOCRIPTINE Cardiomyopathies Cardiology and Cardiovascular Medicine business |
| Zdroj: | European Heart Journal, 35(32), 2165-2173. Oxford University Press European heart journal, 35(32), 2165-2173. Oxford University Press van Spaendonck-Zwarts, K Y, Posafalvi, A, van den Berg, M P, Hilfiker-Kleiner, D, Bollen, I A E, Sliwa, K, Alders, M, Almomani, R, van Langen, I M, van der Meer, P, Sinke, R J, van der Velden, J, van Veldhuisen, D J, van Tintelen, J P & Jongbloed, J D H 2014, ' Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy ', European Heart Journal, vol. 35, no. 32, pp. 2165-2173 . https://doi.org/10.1093/eurheartj/ehu050 |
| ISSN: | 0195-668X |
| DOI: | 10.1093/eurheartj/ehu050 |
| Popis: | Aim Peripartum cardiomyopathy (PPCM) can be an initial manifestation of familial dilated cardiomyopathy (DCM). We aimed to identify mutations in families that could underlie their PPCM and DCM.Methods and results We collected 18 families with PPCM and DCM cases from various countries. We studied the clinical characteristics of the PPCM patients and affected relatives, and applied a targeted next-generation sequencing (NGS) approach to detect mutations in 48 genes known to be involved in inherited cardiomyopathies. We identified 4 pathogenic mutations in 4 of 18 families (22%): 3 in TTN and 1 in BAG3. In addition, we identified 6 variants of unknown clinical significance that may be pathogenic in 6 other families (33%): 4 in TTN, 1 in TNNC1, and 1 in MYH7. Measurements of passive force in single cardiomyocytes and titin isoform composition potentially support an upgrade of one of the variants of unknown clinical significance in TTN to a pathogenic mutation. Only 2 of 20 PPCM cases in these families showed the recovery of left ventricular function.Conclusion Targeted NGS shows that potentially causal mutations in cardiomyopathy-related genes are common in families with both PPCM and DCM. This supports the earlier finding that PPCM can be part of familial DCM. Our cohort is particularly characterized by a high proportion of TTN mutations and a low recovery rate in PPCM cases. |
| Databáze: | OpenAIRE |
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