POPDC2 a novel susceptibility gene for conduction disorders.

Journal of Molecular and Cellular Cardiology
Susanne RinnéNiels Decher

Abstract

Despite recent progress in the understanding of cardiac ion channel function and its role in inherited forms of ventricular arrhythmias, the molecular basis of cardiac conduction disorders often remains unresolved. We aimed to elucidate the genetic background of familial atrioventricular block (AVB) using a whole exome sequencing (WES) approach. In monozygotic twins with a third-degree AVB and in another, unrelated family with first-degree AVB, we identified a heterozygous nonsense mutation in the POPDC2 gene causing a premature stop at position 188 (POPDC2W188⁎), deleting parts of its cAMP binding-domain. Popeye-domain containing (POPDC) proteins are predominantly expressed in the skeletal muscle and the heart, with particularly high expression of POPDC2 in the sinoatrial node of the mouse. We now show by quantitative PCR experiments that in the human heart the POPDC-modulated two-pore domain potassium (K2P) channel TREK-1 is preferentially expressed in the atrioventricular node. Co-expression studies in Xenopus oocytes revealed that POPDC2W188⁎ causes a loss-of-function with impaired TREK-1 modulation. Consistent with the high expression level of POPDC2 in the murine sinoatrial node, POPDC2W188⁎ knock-in mice displayed stress...Continue Reading

Citations

Dec 2, 2020·Journal of Cardiovascular Development and Disease·Laura Fedele, Thomas Brand
May 6, 2021·Journal of Cardiovascular Development and Disease·Drew NassalThomas J Hund
Aug 28, 2021·International Journal of Molecular Sciences·Miklós LengyelGábor Czirják
Oct 27, 2021·Physiological Reviews·Katrina F OstromRennolds S Ostrom
Dec 23, 2021·Cerebral Cortex·Mahesh Shivarama ShettyTed Abel
Jan 26, 2022·The Journal of Gene Medicine·Anwar UllahMuhammad Umair

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