TRPM4 mutations to cause autosomal recessive and not autosomal dominant Brugada type 1 syndrome

European Journal of Medical Genetics
Alexandre JaninGilles Millat

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

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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
Jan 1, 2021·Cardiovascular Therapeutics·Mohamed-Yassine Amarouch, Jaouad El Hilaly
May 11, 2021·Frontiers in Cardiovascular Medicine·Michelle M MonaskyCarlo Pappone

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