Skip to Content
Merck
  • H1153Y-KCNH2 Mutation Identified in a Sudden Arrhythmic Death Syndrome Case Alters Channel Gating.

H1153Y-KCNH2 Mutation Identified in a Sudden Arrhythmic Death Syndrome Case Alters Channel Gating.

International journal of molecular sciences (2021-09-11)
Audrey Farrugia, Kevin Rollet, Jérome Sinniger, Susana Brun, Caroline Spenle, Bertrand Ludes, Omar Taleb, Ayikoe Guy Mensah-Nyagan
ABSTRACT

Long QT syndrome is one of the most common hereditary channelopathies inducing fatal arrhythmias and sudden cardiac death. We identified in a sudden arrhythmic death syndrome case a C-term KCNH2 mutation (c.3457C > T; p.His1153Tyr) classified as variant of unknown significance and functional impact. Heterologous expression in HEK293 cells combined with western-blot, flow-cytometry, immunocytochemical and microscope analyses shows no modification of channel trafficking to the cell membrane. Electrophysiological studies reveal that the mutation causes a loss of HERG channel function through an alteration of channel biophysical properties that reduces the current density leading to LQT2. These results provide the first functional evidence for H1153Y-KCNH2 mutation-induced abnormal channel properties. They concur with previous biophysical and clinical presentations of a survived patient with another variant that is G1036D. Therefore, the present report importantly highlights the potential severity of variants that may have useful implications for treatment, surveillance, and follow-up of LQT2 patients.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Potassium Channel Kv11.1 Extracellular antibody produced in rabbit, affinity isolated antibody, lyophilized powder
Pricing and availability is not currently available.
Sigma-Aldrich
Cell Dissociation Solution Non-enzymatic 1x, Prepared in phosphate buffered saline without calcium and magnesium, sterile-filtered, BioReagent, suitable for cell culture
Pricing and availability is not currently available.