Case Report: Loss-of-function TRPM4 mutation p.L91Δ implicated in progressive cardiac conduction defect
Articles > Article · 2025
Authors: Anne-Flore Hämmerli, Daniela Ross-Kaschitza, Prakash Arullampalam, Anna Shestak, Jimmy Jyh-Ming Juang, Nada El Makhzen, Bianca Sol Soloaga Ricciardi, Alexandre François Edmond Bokhobza, Jean-Sébastien Rougier, Elena V. Zaklyazminskaya, Jacek Gajek, Can HASDEMİR, Hugues Abriel
Frontiers in Physiology, International, WoS, 2025, vol 16, pp 1681438-1681438
DOI: 10.3389/fphys.2025.1681438
Summary
Background: gene can cause familial cases of progressive cardiac conduction defects (PCCDs). Methods and results: Genetic testing was performed using whole-exome sequencing (WES). Modified human embryonic kidney cells overexpressing either wild-type or the variant p.L91Δ of human TRPM4 were used to investigate the biochemical and functional consequences of this deletion. Western blot and biotinylation experiments revealed a significant reduction in the expression of the mutant channel compared with the wild-type. Functional experiments using the patch-clamp approach demonstrated a significant decrease in TRPM4 current, consistent with the biochemical observations. Conclusion: The new TRPM4 in-frame deletion, p.L91Δ, identified in two unrelated patients with a consistent phenotype, causes a significant decrease in channel expression, leading to its loss of function in the heterologous expression system. These findings further exemplify the role of TRPM4 in genetic cardiac channelopathies.