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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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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. |
format | Online Article Text |
id | pubmed-3559649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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