HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy.
作者： Annalisa Milano , Alexa M.C. Vermeer , Elisabeth M. Lodder , Julien Barc , Arie O. Verkerk
DOI: 10.1016/J.JACC.2014.05.045
关键词:
摘要: Abstract Background Familial forms of primary sinus bradycardia have sometimes been attributed to mutations in HCN4, SCN5A, and ANK2. In these studies, no structural cardiac alterations were reported mutation carriers. However, a cluster reports the literature describe patients presenting with association left ventricular noncompaction cardiomyopathy (LVNC), pointing shared genetic cause. Objectives This study sought identify defect underlying combined clinical presentation LVNC, hypothesizing that 2 abnormalities common Methods Exome sequencing was carried out cousins from index family affected by bradycardia–LVNC phenotype; variants thus identified subsequently overlaid chromosomal regions among 5 members using single nucleotide polymorphism array analysis. Results The linkage analysis exome 11 novel cousins. One these, p.Gly482Arg segregated LVNC phenotype entire family. Subsequent screening HCN4 3 additional families same combination each. electrophysiological all found showed more negative voltage dependence activation, consistent observed bradycardia. Conclusions Although previously linked bradycardia, our provides first evidence knowledge this ion channel gene also may be associated myocardium.
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