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Molecular Genetics and Functional Anomalies in a Series of 248 Brugada Cases with 11 Mutations in the TRPM4 Channel

Brugada syndrome (BrS) is a condition defined by ST-segment alteration in right precordial leads and a risk of sudden death. Because BrS is often associated with right bundle branch block and the TRPM4 gene is involved in conduction blocks, we screened TRPM4 for anomalies in BrS cases. The DNA of 24...

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Autores principales: Liu, Hui, Chatel, Stéphanie, Simard, Christophe, Syam, Ninda, Salle, Laurent, Probst, Vincent, Morel, Julie, Millat, Gilles, Lopez, Michel, Abriel, Hugues, Schott, Jean-Jacques, Guinamard, Romain, Bouvagnet, Patrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559649/
https://www.ncbi.nlm.nih.gov/pubmed/23382873
http://dx.doi.org/10.1371/journal.pone.0054131
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author Liu, Hui
Chatel, Stéphanie
Simard, Christophe
Syam, Ninda
Salle, Laurent
Probst, Vincent
Morel, Julie
Millat, Gilles
Lopez, Michel
Abriel, Hugues
Schott, Jean-Jacques
Guinamard, Romain
Bouvagnet, Patrice
author_facet Liu, Hui
Chatel, Stéphanie
Simard, Christophe
Syam, Ninda
Salle, Laurent
Probst, Vincent
Morel, Julie
Millat, Gilles
Lopez, Michel
Abriel, Hugues
Schott, Jean-Jacques
Guinamard, Romain
Bouvagnet, Patrice
author_sort Liu, Hui
collection PubMed
description Brugada syndrome (BrS) is a condition defined by ST-segment alteration in right precordial leads and a risk of sudden death. Because BrS is often associated with right bundle branch block and the TRPM4 gene is involved in conduction blocks, we screened TRPM4 for anomalies in BrS cases. The DNA of 248 BrS cases with no SCN5A mutations were screened for TRPM4 mutations. Among this cohort, 20 patients had 11 TRPM4 mutations. Two mutations were previously associated with cardiac conduction blocks and 9 were new mutations (5 absent from ∼14′000 control alleles and 4 statistically more prevalent in this BrS cohort than in control alleles). In addition to Brugada, three patients had a bifascicular block and 2 had a complete right bundle branch block. Functional and biochemical studies of 4 selected mutants revealed that these mutations resulted in either a decreased expression (p.Pro779Arg and p.Lys914X) or an increased expression (p.Thr873Ile and p.Leu1075Pro) of TRPM4 channel. TRPM4 mutations account for about 6% of BrS. Consequences of these mutations are diverse on channel electrophysiological and cellular expression. Because of its effect on the resting membrane potential, reduction or increase of TRPM4 channel function may both reduce the availability of sodium channel and thus lead to BrS.
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spelling pubmed-35596492013-02-04 Molecular Genetics and Functional Anomalies in a Series of 248 Brugada Cases with 11 Mutations in the TRPM4 Channel Liu, Hui Chatel, Stéphanie Simard, Christophe Syam, Ninda Salle, Laurent Probst, Vincent Morel, Julie Millat, Gilles Lopez, Michel Abriel, Hugues Schott, Jean-Jacques Guinamard, Romain Bouvagnet, Patrice PLoS One Research Article Brugada syndrome (BrS) is a condition defined by ST-segment alteration in right precordial leads and a risk of sudden death. Because BrS is often associated with right bundle branch block and the TRPM4 gene is involved in conduction blocks, we screened TRPM4 for anomalies in BrS cases. The DNA of 248 BrS cases with no SCN5A mutations were screened for TRPM4 mutations. Among this cohort, 20 patients had 11 TRPM4 mutations. Two mutations were previously associated with cardiac conduction blocks and 9 were new mutations (5 absent from ∼14′000 control alleles and 4 statistically more prevalent in this BrS cohort than in control alleles). In addition to Brugada, three patients had a bifascicular block and 2 had a complete right bundle branch block. Functional and biochemical studies of 4 selected mutants revealed that these mutations resulted in either a decreased expression (p.Pro779Arg and p.Lys914X) or an increased expression (p.Thr873Ile and p.Leu1075Pro) of TRPM4 channel. TRPM4 mutations account for about 6% of BrS. Consequences of these mutations are diverse on channel electrophysiological and cellular expression. Because of its effect on the resting membrane potential, reduction or increase of TRPM4 channel function may both reduce the availability of sodium channel and thus lead to BrS. Public Library of Science 2013-01-30 /pmc/articles/PMC3559649/ /pubmed/23382873 http://dx.doi.org/10.1371/journal.pone.0054131 Text en © 2013 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Liu, Hui
Chatel, Stéphanie
Simard, Christophe
Syam, Ninda
Salle, Laurent
Probst, Vincent
Morel, Julie
Millat, Gilles
Lopez, Michel
Abriel, Hugues
Schott, Jean-Jacques
Guinamard, Romain
Bouvagnet, Patrice
Molecular Genetics and Functional Anomalies in a Series of 248 Brugada Cases with 11 Mutations in the TRPM4 Channel
title Molecular Genetics and Functional Anomalies in a Series of 248 Brugada Cases with 11 Mutations in the TRPM4 Channel
title_full Molecular Genetics and Functional Anomalies in a Series of 248 Brugada Cases with 11 Mutations in the TRPM4 Channel
title_fullStr Molecular Genetics and Functional Anomalies in a Series of 248 Brugada Cases with 11 Mutations in the TRPM4 Channel
title_full_unstemmed Molecular Genetics and Functional Anomalies in a Series of 248 Brugada Cases with 11 Mutations in the TRPM4 Channel
title_short Molecular Genetics and Functional Anomalies in a Series of 248 Brugada Cases with 11 Mutations in the TRPM4 Channel
title_sort molecular genetics and functional anomalies in a series of 248 brugada cases with 11 mutations in the trpm4 channel
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559649/
https://www.ncbi.nlm.nih.gov/pubmed/23382873
http://dx.doi.org/10.1371/journal.pone.0054131
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