Disease-associated HCN4 V759I variant is not sufficient to impair cardiac pacemaking.

ABSTRACT: The hyperpolarization-activated cation current I_f is a key determinant for cardiac pacemaker activity. It is conducted by subunits of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel family, of which HCN4 is predominant in mammalian heart. Both loss-of-function and gain-of-function mutations of the HCN4 gene are associated with sinus node dysfunction in humans; however, their functional impact is not fully understood yet. Here, we sought to characterize a HCN4 V759I variant detected in a patient with a family history of sick sinus syndrome. The genomic analysis yielded a mono-allelic HCN4 V759I variant in a 49-year-old woman presenting with a family history of sick sinus syndrome. This HCN4 variant was previously classified as putatively pathogenic because g

SUBMITTER: Erlenhardt N 

PROVIDER: S-EPMC7691308 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature