PMID- 30910390
OWN - NLM
STAT- MEDLINE
DCOM- 20200506
LR  - 20200506
IS  - 1876-4738 (Electronic)
IS  - 0914-5087 (Linking)
VI  - 73
IP  - 5
DP  - 2019 May
TI  - Recent understanding of clinical sequencing and gene-based risk stratification in 
      inherited primary arrhythmia syndrome.
PG  - 335-342
LID - S0914-5087(19)30015-2 [pii]
LID - 10.1016/j.jjcc.2019.01.009 [doi]
AB  - Inherited primary arrhythmia syndromes (IPAS) may result in ventricular 
      tachycardia or ventricular fibrillation by some genetic disorders, leading to 
      sudden cardiac death. IPAS are also called "channelopathies" since many of these 
      are caused by an abnormality in myocardial ion channels. Congenital long-QT 
      syndrome (LQTS) is the most well documented IPAS, which may be seen in 0.1% of 
      the general population. More than 15 disease-causing genes have been identified 
      in almost 70% of LQTS patients and genetic testing is well applied to not only 
      clinical diagnosis but also risk stratification and gene-based therapeutic 
      strategy for each person with LQTS. Thus, in LQTS, gene-based personalized 
      medicine can be realized. Unlike the LQTS, genetic testing for the Brugada 
      syndrome (BrS) is still controversial since only 20% of patients can be 
      identified with the causing gene mutations, most of which are in SCN5A. 
      Furthermore, even in the SCN5A mutation-positive carriers, their phenotypes are 
      not completely consistent with BrS, but may cause other IPAS including LQTS, 
      cardiac conduction defect, sick sinus syndrome, and dilated cardiomyopathy. On 
      the other hand, a recent Japanese BrS registry demonstrated that the pore-region 
      mutations in SCN5A are significantly associated with a risk of lethal cardiac 
      events. Furthermore, a genome-wide association study revealed that a common 
      variant in SCN10A or HEY2 in addition to SCN5A is associated with BrS, thus, BrS 
      may not be a monogenic Mendelian disease but probably an oligogenic disease. The 
      purpose of this review is to describe the basic genetic and pathophysiological 
      findings of the IPAS, particularly LQTS and Brugada syndrome, and to outline a 
      rational approach to genetic testing, management, and family screening.
CI  - Copyright (c) 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All 
      rights reserved.
FAU - Aiba, Takeshi
AU  - Aiba T
AD  - Department of Advanced Arrhythmia and Translational Medical Science, National 
      Cerebral and Cardiovascular Center, Osaka, Japan. Electronic address: 
      aiba@ncvc.go.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190323
PL  - Netherlands
TA  - J Cardiol
JT  - Journal of cardiology
JID - 8804703
SB  - IM
MH  - Brugada Syndrome/*genetics
MH  - Genetic Testing
MH  - Humans
MH  - Long QT Syndrome/*genetics
MH  - Risk Assessment
MH  - Tachycardia, Ventricular/*genetics
OTO - NOTNLM
OT  - Arrhythmias
OT  - Diagnosis
OT  - Genetics
OT  - Ion channels
OT  - Sudden cardiac death
EDAT- 2019/03/27 06:00
MHDA- 2020/05/07 06:00
CRDT- 2019/03/27 06:00
PHST- 2019/01/04 00:00 [received]
PHST- 2019/01/07 00:00 [accepted]
PHST- 2019/03/27 06:00 [pubmed]
PHST- 2020/05/07 06:00 [medline]
PHST- 2019/03/27 06:00 [entrez]
AID - S0914-5087(19)30015-2 [pii]
AID - 10.1016/j.jjcc.2019.01.009 [doi]
PST - ppublish
SO  - J Cardiol. 2019 May;73(5):335-342. doi: 10.1016/j.jjcc.2019.01.009. Epub 2019 Mar 
      23.