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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A novel disease gene for Brugada syndrome: Sarcolemmal membrane-associated protein gene mutations impair intracellular trafficking of hNav1.5
Circulation: Arrhythmia and Electrophysiology, Volume 5, No. 6, Year 2012
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Description
Background: Mutations in genes including SCN5A encoding the α-subunit of the cardiac sodium channel (hNav1.5) cause Brugada syndrome via altered function of cardiac ion channels, but more than two-thirds of Brugada syndrome remains pathogenetically elusive. T-tubules and sarcoplasmic reticulum are essential in excitation of cardiomyocytes, and sarcolemmal membrane-associated protein (SLMAP) is a protein of unknown function localizing at T-tubules and sarcoplasmic reticulum. Methods and Results: We analyzed 190 unrelated Brugada syndrome patients for mutations in SLMAP. Two missense mutations, Val269Ile and Glu710Ala, were found in heterozygous state in 2 patients but were not found in healthy individuals. Membrane surface expression of hNav1.5 in the transfected cells was affected by the mutations, and silencing of mutant SLMAP by small interfering RNA rescued the surface expression of hNav1.5. Whole-cell patch-clamp recordings of hNav1.5-expressing cells transfected with mutant SLMAP confirmed the reduced hNav1.5 current. Conclusions: The mutations in SLMAP may cause Brugada syndrome via modulating the intracellular trafficking of hNav1.5 channel. © 2012 American Heart Association, Inc.
Authors & Co-Authors
Ishikawa, Taisuke
Japan, Tokyo
Tokyo Medical and Dental University
Sato, Akinori
Japan, Tokyo
Tokyo Medical and Dental University
Japan, Niigata
Niigata University, Graduate School of Medical and Dental Science
Marcou, Cherisse A.
United States, Rochester
Mayo Clinic
Tester, David J.
United States, Rochester
Mayo Clinic
Ackerman, Michael John
United States, Rochester
Mayo Clinic
CROTTI, L.
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Italy, Pavia
Università Degli Studi Di Pavia
Italy, Pavia
Fondazione Irccs Policlinico San Matteo
Schwartz, Peter J.
Italy, Pavia
Università Degli Studi Di Pavia
Italy, Pavia
Fondazione Irccs Policlinico San Matteo
South Africa, Cape Town
University of Cape Town
South Africa, Stellenbosch
Stellenbosch University
Saudi Arabia, Riyadh
College of Medicine
On, Young-keun
South Korea, Suwon
Skku School of Medicine
Park, Jeong-euy
Unknown Affiliation
Nakamura, Kazufumi
Japan, Okayama
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hiraoka, Masayasu
Japan, Tokyo
Tokyo Medical and Dental University
Nakazawa, Kiyoshi
Japan, Kawasaki
Asao General Hospital
Sakurada, Harumizu
Japan, Tokyo
Tokyo Metropolitan Hiroo Hospital
Arimura, Takuro
Japan, Tokyo
Tokyo Medical and Dental University
Makita, Naomasa
Japan, Nagasaki
Graduate School of Biomedical Sciences
Kimura, Akinori
Japan, Tokyo
Tokyo Medical and Dental University
Statistics
Citations: 94
Authors: 16
Affiliations: 14
Identifiers
Doi:
10.1161/CIRCEP.111.969972
ISSN:
19413149
e-ISSN:
19413084
Research Areas
Genetics And Genomics
Noncommunicable Diseases