Targeted next generation sequencing in a young population with suspected inherited malignant cardiac arrhythmias
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| Title: | Targeted next generation sequencing in a young population with suspected inherited malignant cardiac arrhythmias |
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| Authors: | Henrik Jensen, Morten Krogh Christiansen, Jens Cosedis Nielsen, Anders Krogh Broendberg, Lisbeth Noerum Pedersen |
| Source: | Eur J Hum Genet Broendberg, A K, Christiansen, M K, Nielsen, J C, Pedersen, L N & Jensen, H K 2018, 'Targeted next generation sequencing in a young population with suspected inherited malignant cardiac arrhythmias', European Journal of Human Genetics, vol. 26, no. 3, pp. 303-313. https://doi.org/10.1038/s41431-017-0060-8 |
| Publisher Information: | Springer Science and Business Media LLC, 2018. |
| Publication Year: | 2018 |
| Subject Terms: | Adult, Male, Ion Channels/genetics, Arrhythmias, Cardiac, Sequence Analysis, DNA, Article, Ion Channels, 3. Good health, 03 medical and health sciences, Arrhythmias, Cardiac/complications, Death, Sudden, Cardiac, 0302 clinical medicine, Gene Frequency, Mutation, Humans, Female, Genetic Testing, Death, Sudden, Cardiac/etiology, Genome-Wide Association Study |
| Description: | Aborted sudden cardiac death in the young often is due to inherited heart disease. However, the clinical phenotype in these patients is not always evident. The aim of this study was to identify pathogenic molecular genetic variants in a population with suspected inherited cardiac arrhythmias. Eligible patients were admitted to Aarhus University Hospital, Denmark during the period 1999-2013 with arrhythmias assumed caused by a hereditary heart disease, and in whom no genotype had been established. We used the Danish national pacemaker and ICD registry to identify this cohort. One third (24/80) of the study population had first-line genetic testing with a targeted next-generation sequencing (NGS) panel, and two-third (56/80) of the study population had second-line genetic testing with NGS where prior Sanger sequencing did not reveal a causative variant. Variants were assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. We included 80 patients. Median age (IQR) was 38 (28-43) years, 54 (68%) were males. First-line genetic testing identified a genetic variant in 33% (8/24) of the cases and second-line genetic testing revealed a variant in 20% (11/56) of the cases. Eleven variants were considered pathogenic, three likely pathogenic and 10 were variants of unknown significance (VUS). Seventeen variants were very rare with a minor allele frequency (MAF) ≤0.02% in all population databases used in the study. Molecular genetic testing of patients with suspected inherited cardiac arrhythmias with NGS identifies a molecular-genetic cause in a significant proportion of patients. |
| Document Type: | Article Other literature type |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/s41431-017-0060-8 |
| Access URL: | https://www.nature.com/articles/s41431-017-0060-8.pdf https://pubmed.ncbi.nlm.nih.gov/29343803 https://www.nature.com/articles/s41431-017-0060-8/ http://europepmc.org/articles/PMC5838968 https://pubmed.ncbi.nlm.nih.gov/29343803/ https://www.ncbi.nlm.nih.gov/pubmed/29343803 https://www.nature.com/articles/s41431-017-0060-8.pdf https://pure.au.dk/ws/files/166761480/s41431_017_0060_8.pdf https://pure.au.dk/ws/files/166761480/s41431_017_0060_8.pdf http://www.scopus.com/inward/record.url?scp=85040706188&partnerID=8YFLogxK https://doi.org/10.1038/s41431-017-0060-8 https://pure.au.dk/portal/en/publications/0e479511-9e52-44c5-ba6d-ece691e2dc98 |
| Rights: | CC BY |
| Accession Number: | edsair.doi.dedup.....daa6eb16f81b6a862ab244436ce1c597 |
| Database: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | Aborted sudden cardiac death in the young often is due to inherited heart disease. However, the clinical phenotype in these patients is not always evident. The aim of this study was to identify pathogenic molecular genetic variants in a population with suspected inherited cardiac arrhythmias. Eligible patients were admitted to Aarhus University Hospital, Denmark during the period 1999-2013 with arrhythmias assumed caused by a hereditary heart disease, and in whom no genotype had been established. We used the Danish national pacemaker and ICD registry to identify this cohort. One third (24/80) of the study population had first-line genetic testing with a targeted next-generation sequencing (NGS) panel, and two-third (56/80) of the study population had second-line genetic testing with NGS where prior Sanger sequencing did not reveal a causative variant. Variants were assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. We included 80 patients. Median age (IQR) was 38 (28-43) years, 54 (68%) were males. First-line genetic testing identified a genetic variant in 33% (8/24) of the cases and second-line genetic testing revealed a variant in 20% (11/56) of the cases. Eleven variants were considered pathogenic, three likely pathogenic and 10 were variants of unknown significance (VUS). Seventeen variants were very rare with a minor allele frequency (MAF) ≤0.02% in all population databases used in the study. Molecular genetic testing of patients with suspected inherited cardiac arrhythmias with NGS identifies a molecular-genetic cause in a significant proportion of patients. |
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| ISSN: | 14765438 10184813 |
| DOI: | 10.1038/s41431-017-0060-8 |