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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Hui Liu, Stéphanie Chatel, Christophe Simard, Ninda Syam, Laurent Salle, Vincent Probst, Julie Morel, Gilles Millat, Michel Lopez, Hugues Abriel, Jean-Jacques Schott, Romain Guinamard, Patrice Bouvagnet
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
Materias:
R
Q
Acceso en línea:https://doaj.org/article/8c664dfcc2d54849bed4c4b23a727a01
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:8c664dfcc2d54849bed4c4b23a727a01
record_format dspace
spelling oai:doaj.org-article:8c664dfcc2d54849bed4c4b23a727a012021-11-18T07:59:35ZMolecular genetics and functional anomalies in a series of 248 Brugada cases with 11 mutations in the TRPM4 channel.1932-620310.1371/journal.pone.0054131https://doaj.org/article/8c664dfcc2d54849bed4c4b23a727a012013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23382873/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Brugada 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.Hui LiuStéphanie ChatelChristophe SimardNinda SyamLaurent SalleVincent ProbstJulie MorelGilles MillatMichel LopezHugues AbrielJean-Jacques SchottRomain GuinamardPatrice BouvagnetPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54131 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hui Liu
Stéphanie Chatel
Christophe Simard
Ninda Syam
Laurent Salle
Vincent Probst
Julie Morel
Gilles Millat
Michel Lopez
Hugues Abriel
Jean-Jacques Schott
Romain Guinamard
Patrice Bouvagnet
Molecular genetics and functional anomalies in a series of 248 Brugada cases with 11 mutations in the TRPM4 channel.
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 article
author Hui Liu
Stéphanie Chatel
Christophe Simard
Ninda Syam
Laurent Salle
Vincent Probst
Julie Morel
Gilles Millat
Michel Lopez
Hugues Abriel
Jean-Jacques Schott
Romain Guinamard
Patrice Bouvagnet
author_facet Hui Liu
Stéphanie Chatel
Christophe Simard
Ninda Syam
Laurent Salle
Vincent Probst
Julie Morel
Gilles Millat
Michel Lopez
Hugues Abriel
Jean-Jacques Schott
Romain Guinamard
Patrice Bouvagnet
author_sort Hui Liu
title 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_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_sort molecular genetics and functional anomalies in a series of 248 brugada cases with 11 mutations in the trpm4 channel.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/8c664dfcc2d54849bed4c4b23a727a01
work_keys_str_mv AT huiliu moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT stephaniechatel moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT christophesimard moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT nindasyam moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT laurentsalle moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT vincentprobst moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT juliemorel moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT gillesmillat moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT michellopez moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT huguesabriel moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT jeanjacquesschott moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT romainguinamard moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
AT patricebouvagnet moleculargeneticsandfunctionalanomaliesinaseriesof248brugadacaseswith11mutationsinthetrpm4channel
_version_ 1718422680408948736