Haplotype-sharing analysis implicates chromosome 7q36 harboring DPP6 in familial idiopathic ventricular fibrillation.
Am J Hum Genet
; 84(4): 468-76, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19285295
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Hidrolases
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Fibrilação Ventricular
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Cromossomos Humanos Par 7
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Canais de Potássio
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Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Holanda