Familial Idiopathic Ventricular Fibrillation Linked to Chromosome 7q36 Harboring DPP6

Pieter G. Postema, Imke Christiaans, Tamara Koopmann, Marielle Alders, Ling Xiao, A. Varró, Connie Bezzina, Stanley Nattel, Arthur Am Wilde

Research output: Contribution to journalArticle

Abstract

Background: Until recently it was impossible to identify presymptomatic family members at risk for fatal events in familial idiopathic ventricular fibrillation (IVF). We uncovered a large IVF-family and linked their arrhythmic events to a new arrhythmia gene on chromosome 7q36: DPP6. Methods and Results: We studied 169 carriers and 195 non-carriers. ECGs and echocardiography were normal. All-cause mortality or IVF/resuscitation occurred in 67 carriers and 7 non-carriers (no IVF/resuscitation). At 62 years of age, 50% of carriers had an event (p<0.001), the youngest 16 years old, males earlier than females (56 vs. 72 years, p<0.001). IVF was always elicited by monomorphic short-coupled extrasystoles from the right ventricular apex/lower free wall and an origin in the Purkinje network was suspected. Expression-studies showed overexpression of DPP6 mRNA in carriers (p<0.01). Expression-studies in non-diseased explanted human hearts showed higher DPP6 mRNA expression in Purkinje fiber than in any other region (p<0.01). Conclusions: A new arrhythmia gene on chromosome 7q36, DPP6, is linked to familial IVF and shows a very malignant phenotype. Short-coupled extrasystoles from the right-ventricular apex/free wall, presumably originating from the Purkinje network, trigger IVF. For the first time, only genetic predisposition can be used as a risk-marker for future events in IVF.

Original languageEnglish
Pages (from-to)413
Number of pages1
JournalJournal of Arrhythmia
Volume27
Issue number4
DOIs
Publication statusPublished - 2011

Fingerprint

Chromosomes
Ventricular Premature Complexes
Resuscitation
Cardiac Arrhythmias
Purkinje Fibers
Messenger RNA
Paroxysmal ventricular fibrillation
Genetic Predisposition to Disease
Genes
Echocardiography
Electrocardiography
Phenotype
Mortality

Keywords

  • DPP6
  • idiopathic ventricular fibrillation
  • Purkinje

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Postema, P. G., Christiaans, I., Koopmann, T., Alders, M., Xiao, L., Varró, A., ... Wilde, A. A. (2011). Familial Idiopathic Ventricular Fibrillation Linked to Chromosome 7q36 Harboring DPP6. Journal of Arrhythmia, 27(4), 413. https://doi.org/10.4020/jhrs.27.OP59_4

Familial Idiopathic Ventricular Fibrillation Linked to Chromosome 7q36 Harboring DPP6. / Postema, Pieter G.; Christiaans, Imke; Koopmann, Tamara; Alders, Marielle; Xiao, Ling; Varró, A.; Bezzina, Connie; Nattel, Stanley; Wilde, Arthur Am.

In: Journal of Arrhythmia, Vol. 27, No. 4, 2011, p. 413.

Research output: Contribution to journalArticle

Postema, PG, Christiaans, I, Koopmann, T, Alders, M, Xiao, L, Varró, A, Bezzina, C, Nattel, S & Wilde, AA 2011, 'Familial Idiopathic Ventricular Fibrillation Linked to Chromosome 7q36 Harboring DPP6', Journal of Arrhythmia, vol. 27, no. 4, pp. 413. https://doi.org/10.4020/jhrs.27.OP59_4
Postema, Pieter G. ; Christiaans, Imke ; Koopmann, Tamara ; Alders, Marielle ; Xiao, Ling ; Varró, A. ; Bezzina, Connie ; Nattel, Stanley ; Wilde, Arthur Am. / Familial Idiopathic Ventricular Fibrillation Linked to Chromosome 7q36 Harboring DPP6. In: Journal of Arrhythmia. 2011 ; Vol. 27, No. 4. pp. 413.
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AB - Background: Until recently it was impossible to identify presymptomatic family members at risk for fatal events in familial idiopathic ventricular fibrillation (IVF). We uncovered a large IVF-family and linked their arrhythmic events to a new arrhythmia gene on chromosome 7q36: DPP6. Methods and Results: We studied 169 carriers and 195 non-carriers. ECGs and echocardiography were normal. All-cause mortality or IVF/resuscitation occurred in 67 carriers and 7 non-carriers (no IVF/resuscitation). At 62 years of age, 50% of carriers had an event (p<0.001), the youngest 16 years old, males earlier than females (56 vs. 72 years, p<0.001). IVF was always elicited by monomorphic short-coupled extrasystoles from the right ventricular apex/lower free wall and an origin in the Purkinje network was suspected. Expression-studies showed overexpression of DPP6 mRNA in carriers (p<0.01). Expression-studies in non-diseased explanted human hearts showed higher DPP6 mRNA expression in Purkinje fiber than in any other region (p<0.01). Conclusions: A new arrhythmia gene on chromosome 7q36, DPP6, is linked to familial IVF and shows a very malignant phenotype. Short-coupled extrasystoles from the right-ventricular apex/free wall, presumably originating from the Purkinje network, trigger IVF. For the first time, only genetic predisposition can be used as a risk-marker for future events in IVF.

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