Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel
dc.contributor.author | Celestino-Soper, Patrícia B. S. | |
dc.contributor.author | Doytchinova, Anisiia | |
dc.contributor.author | Steiner, Hillel A. | |
dc.contributor.author | Uradu, Andrea | |
dc.contributor.author | Lynnes, Ty C. | |
dc.contributor.author | Groh, William J. | |
dc.contributor.author | Miller, John M. | |
dc.contributor.author | Lin, Hai | |
dc.contributor.author | Gao, Hongyu | |
dc.contributor.author | Wang, Zhiping | |
dc.contributor.author | Liu, Yunlong | |
dc.contributor.author | Chen, Peng-Sheng | |
dc.contributor.author | Vatta, Matteo | |
dc.contributor.department | Department of Medical and Molecular Genetics, IU School of Medicine | en_US |
dc.date.accessioned | 2017-01-04T22:40:43Z | |
dc.date.available | 2017-01-04T22:40:43Z | |
dc.date.issued | 2015 | |
dc.description.abstract | BACKGROUND: The etiology of conduction disturbances necessitating permanent pacemaker (PPM) implantation is often unknown, although familial aggregation of PPM (faPPM) suggests a possible genetic basis. We developed a pan-cardiovascular next generation sequencing (NGS) panel to genetically characterize a selected cohort of faPPM. MATERIALS AND METHODS: We designed and validated a custom NGS panel targeting the coding and splicing regions of 246 genes with involvement in cardiac pathogenicity. We enrolled 112 PPM patients and selected nine (8%) with faPPM to be analyzed by NGS. RESULTS: Our NGS panel covers 95% of the intended target with an average of 229x read depth at a minimum of 15-fold depth, reaching a SNP true positive rate of 98%. The faPPM patients presented with isolated cardiac conduction disease (ICCD) or sick sinus syndrome (SSS) without overt structural heart disease or identifiable secondary etiology. Three patients (33.3%) had heterozygous deleterious variants previously reported in autosomal dominant cardiac diseases including CCD: LDB3 (p.D117N) and TRPM4 (p.G844D) variants in patient 4; TRPM4 (p.G844D) and ABCC9 (p.V734I) variants in patient 6; and SCN5A (p.T220I) and APOB (p.R3527Q) variants in patient 7. CONCLUSION: FaPPM occurred in 8% of our PPM clinic population. The employment of massive parallel sequencing for a large selected panel of cardiovascular genes identified a high percentage (33.3%) of the faPPM patients with deleterious variants previously reported in autosomal dominant cardiac diseases, suggesting that genetic variants may play a role in faPPM. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Celestino-Soper, P. B. S., Doytchinova, A., Steiner, H. A., Uradu, A., Lynnes, T. C., Groh, W. J., … Vatta, M. (2015). Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel. PLoS ONE, 10(12), e0143588. http://doi.org/10.1371/journal.pone.0143588 | en_US |
dc.identifier.issn | 1932-6203 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/11761 | |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science (PloS) | en_US |
dc.relation.isversionof | 10.1371/journal.pone.0143588 | en_US |
dc.relation.journal | PloS One | en_US |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | PMC | en_US |
dc.subject | Brugada Syndrome | en_US |
dc.subject | genetics | en_US |
dc.subject | Genetic Variation | en_US |
dc.subject | High-Throughput Nucleotide Sequencing | en_US |
dc.subject | methods | en_US |
dc.subject | Sequence Analysis, DNA | en_US |
dc.subject | Sick Sinus Syndrome | en_US |
dc.title | Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel | en_US |
dc.type | Article | en_US |
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