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Next-generation sequencing of AV nodal reentrant tachycardia patients identifies broad spectrum of variants in ion channel genes.

Andreasen, L; Ahlberg, G; Tang, C; Andreasen, C; Hartmann, JP; Tfelt-Hansen, J; Behr, ER; Pehrson, S; Haunsø, S; LuCamp, ; et al. Andreasen, L; Ahlberg, G; Tang, C; Andreasen, C; Hartmann, JP; Tfelt-Hansen, J; Behr, ER; Pehrson, S; Haunsø, S; LuCamp; Weeke, PE; Jespersen, T; Olesen, MS; Svendsen, JH (2018) Next-generation sequencing of AV nodal reentrant tachycardia patients identifies broad spectrum of variants in ion channel genes. Eur J Hum Genet, 26 (5). pp. 660-668. ISSN 1476-5438 https://doi.org/10.1038/s41431-017-0092-0
SGUL Authors: Behr, Elijah Raphael

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Abstract

Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients <40 years of age. Familial clustering, early onset of symptoms and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases. Next-generation sequencing of 67 genes was applied to the DNA profile of 298 AVNRT patients and 10 AVNRT family members using HaloPlex Target Enrichment System. In total, we identified 229 variants in 60 genes; 215 missenses, four frame shifts, four codon deletions, three missense and splice sites, two stop-gain variants, and one start-lost variant. Sixty-five of these were not present in the Exome Aggregation Consortium (ExAC) database. Furthermore, we report two AVNRT families with co-segregating variants. Seventy-five of 284 AVNRT patients (26.4%) and three family members to different AVNRT probands had one or more variants in genes affecting the sodium handling. Fifty-four out of 284 AVNRT patients (19.0%) had variants in genes affecting the calcium handling of the heart. We furthermore find a large proportion of variants in the HCN1-4 genes. We did not detect a significant enrichment of rare variants in the tested genes. This could be an indication that AVNRT might be an electrical arrhythmic disease with abnormal sodium and calcium handling.

Item Type: Article
Additional Information: This is a post-peer-review, pre-copyedit version of an article published in European Journal of Human Genetics. The final authenticated version is available online at: http://dx.doi.org/10.1038/s41431-017-0092-0
Keywords: Genetics & Heredity, 0604 Genetics
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cardiac (INCCCA)
Journal or Publication Title: Eur J Hum Genet
ISSN: 1476-5438
Language: eng
Dates:
DateEvent
May 2018Published
2 February 2018Published Online
5 December 2017Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
DFF-1331-00313BDanish Council for Independent ResearchUNSPECIFIED
PubMed ID: 29396561
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109637
Publisher's version: https://doi.org/10.1038/s41431-017-0092-0

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