Abstract
Cardiac channelopathies, mainly Long QT and Brugada syndromes, are genetic disorders for which genotype/phenotypes relationships remains to be improved. To provide new insights into the Brugada syndrome pathophysiology, a mutational study was performed on a 64-year-old man presented with isolated exertional dyspnea (NYHA class: II-III), hypertension, chronic kidney disease, coronary disease, an electrocardiogram suggesting a Brugada type 1-like pattern with ST-segment elevation in leads V1-V2. Molecular diagnosis study was performed using molecular strategy based on the sequencing of a panel of 19 Brugada-associated genes. The proband was carrier of 2 TRPM4 null alleles [IVS9+1G > A and p. Trp525X] resulting in the absence of functional hTRPM4 proteins. Due to this unexpected genotype, meta-analysis of previously reported TRPM4 variations associated with cardiac pathologies was performed using ACMG guidelines. All were detected in a heterozygous status. This additional meta-analysis indicated that most of them could not be considered definitely as pathogen. In conclusion, our study reports, for the first time, identification of compound heterozygous TRPM4 null mutations in a proband with, at an arrhythmogenic level, only a Brug...Continue Reading
References
Nov 15, 1992·Journal of the American College of Cardiology·P Brugada, J Brugada
May 23, 2002·Cell·Pierre LaunayJean Pierre Kinet
Sep 4, 2009·The Journal of Clinical Investigation·Martin KruseOlaf Pongs
Jun 22, 2010·Circulation. Cardiovascular Genetics·Hui LiuPatrice Bouvagnet
Aug 4, 2010·The Journal of Clinical Investigation·Ilka MatharMarc Freichel
Sep 3, 2011·Human Mutation·Birgit StallmeyerEric Schulze-Bahr
Jan 8, 2013·Frontiers in Physiology·Guillaume DuthoitJean-Louis Hébert
Feb 6, 2013·PloS One·Hui LiuPatrice Bouvagnet
Apr 12, 2014·Current Opinion in Pharmacology·Martin Kruse, Olaf Pongs
Dec 23, 2014·PloS One·Marie DemionSylvain Richard
Feb 5, 2015·Human Molecular Genetics·Solena Le ScouarnecRichard Redon
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Apr 8, 2015·DNA and Cell Biology·Gilles MillatDominique Bozon
Dec 22, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Valérie ChanavatGilles Millat
Jan 29, 2016·International Journal of Cardiology·Xavier DaumyJean-Jacques Schott
Nov 5, 2016·Nature Reviews. Cardiology·Juan SieiraPedro Brugada
May 12, 2017·Cardiology·Francesca GualandiAlessandra Ferlini
Citations
Oct 2, 2020·International Journal of Molecular Sciences·Oscar CampuzanoRamon Brugada
Aug 23, 2020·International Journal of Molecular Sciences·Michelle M MonaskyCarlo Pappone
Mar 4, 2020·International Journal of Molecular Sciences·Michelle M MonaskyCarlo Pappone
Jun 19, 2020·Journal of Clinical Medicine·Oscar CampuzanoRamon Brugada
Jan 1, 2021·Cardiovascular Therapeutics·Mohamed-Yassine Amarouch, Jaouad El Hilaly
May 6, 2021·Cell Reports Medicine·Mel Lina Pinsach-AbuinSara Pagans
May 8, 2021·BioMed Research International·Yi DongRong Xiang
May 11, 2021·Frontiers in Cardiovascular Medicine·Michelle M MonaskyCarlo Pappone