Alders_2009_Am.J.Hum.Genet_84_468

Reference

Title : Haplotype-sharing analysis implicates chromosome 7q36 harboring DPP6 in familial idiopathic ventricular fibrillation. - Alders_2009_Am.J.Hum.Genet_84_468
Author(s) : Alders M , Koopmann TT , Christiaans I , Postema PG , Beekman L , Tanck MW , Zeppenfeld K , Loh P , Koch KT , Demolombe S , Mannens MM , Bezzina CR , Wilde AA
Ref : American Journal of Human Genetics , 84 :468 , 2009
Abstract :

Idiopathic Ventricular Fibrillation (IVF) is defined as spontaneous VF without any known structural or electrical heart disease. A family history is present in up to 20% of probands with the disorder, suggesting that at least a subset of IVF is hereditary. A genome-wide haplotype-sharing analysis was performed for identification of the responsible gene in three distantly related families in which multiple individuals died suddenly or were successfully resuscitated at young age. We identified a haplotype, on chromosome 7q36, that was conserved in these three families and was also shared by 7 of 42 independent IVF patients. The shared chromosomal segment harbors part of the DPP6 gene, which encodes a putative component of the transient outward current in the heart. We demonstrated a 20-fold increase in DPP6 mRNA levels in the myocardium of carriers as compared to controls. Clinical evaluation of 84 risk-haplotype carriers and 71 noncarriers revealed no ECG or structural parameters indicative of cardiac disease. Penetrance of IVF was high; 50% of risk-haplotype carriers experienced (aborted) sudden cardiac death before the age of 58 years. We propose DPP6 as a gene for IVF and increased DPP6 expression as the likely pathogenetic mechanism.

PubMedSearch : Alders_2009_Am.J.Hum.Genet_84_468
PubMedID: 19285295
Gene_locus related to this paper: human-DPP6

Citations formats

Alders M, Koopmann TT, Christiaans I, Postema PG, Beekman L, Tanck MW, Zeppenfeld K, Loh P, Koch KT, Demolombe S, Mannens MM, Bezzina CR, Wilde AA (2009)
Haplotype-sharing analysis implicates chromosome 7q36 harboring DPP6 in familial idiopathic ventricular fibrillation.
American Journal of Human Genetics 84 :468

Alders M, Koopmann TT, Christiaans I, Postema PG, Beekman L, Tanck MW, Zeppenfeld K, Loh P, Koch KT, Demolombe S, Mannens MM, Bezzina CR, Wilde AA (2009)
American Journal of Human Genetics 84 :468