TY - JOUR
T1 - Genetic testing in heritable cardiac arrhythmia syndromes
T2 - Differentiating pathogenic mutations from background genetic noise
AU - Giudicessi, John R.
AU - Ackerman, Michael J.
PY - 2013/1
Y1 - 2013/1
N2 - PURPOSE OF REVIEW: In this review, we summarize the basic principles governing rare variant interpretation in the heritable cardiac arrhythmia syndromes, focusing on recent advances that have led to disease-specific approaches to the interpretation of positive genetic testing results. RECENT FINDINGS: Elucidation of the genetic substrates underlying heritable cardiac arrhythmia syndromes has unearthed new arrhythmogenic mechanisms and given rise to a number of clinically meaningful genotype-phenotype correlations. As such, genetic testing for these disorders now carries important diagnostic, prognostic, and therapeutic implications. Recent large-scale systematic studies designed to explore the background genetic 'noise' rate associated with these genetic tests have provided important insights and enhanced how positive genetic testing results are interpreted for these potentially lethal, yet highly treatable, cardiovascular disorders. SUMMARY: Clinically available genetic tests for heritable cardiac arrhythmia syndromes allow the identification of potentially at-risk family members and contribute to the risk-stratification and selection of therapeutic interventions in affected individuals. The systematic evaluation of the 'signal-to-noise' ratio associated with these genetic tests has proven critical and essential to assessing the probability that a given variant represents a rare pathogenic mutation or an equally rare, yet innocuous, genetic bystander.
AB - PURPOSE OF REVIEW: In this review, we summarize the basic principles governing rare variant interpretation in the heritable cardiac arrhythmia syndromes, focusing on recent advances that have led to disease-specific approaches to the interpretation of positive genetic testing results. RECENT FINDINGS: Elucidation of the genetic substrates underlying heritable cardiac arrhythmia syndromes has unearthed new arrhythmogenic mechanisms and given rise to a number of clinically meaningful genotype-phenotype correlations. As such, genetic testing for these disorders now carries important diagnostic, prognostic, and therapeutic implications. Recent large-scale systematic studies designed to explore the background genetic 'noise' rate associated with these genetic tests have provided important insights and enhanced how positive genetic testing results are interpreted for these potentially lethal, yet highly treatable, cardiovascular disorders. SUMMARY: Clinically available genetic tests for heritable cardiac arrhythmia syndromes allow the identification of potentially at-risk family members and contribute to the risk-stratification and selection of therapeutic interventions in affected individuals. The systematic evaluation of the 'signal-to-noise' ratio associated with these genetic tests has proven critical and essential to assessing the probability that a given variant represents a rare pathogenic mutation or an equally rare, yet innocuous, genetic bystander.
KW - Brugada syndrome
KW - genetics
KW - ion channels
KW - long QT syndrome
KW - sudden death
UR - http://www.scopus.com/inward/record.url?scp=84871630327&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871630327&partnerID=8YFLogxK
U2 - 10.1097/HCO.0b013e32835b0a41
DO - 10.1097/HCO.0b013e32835b0a41
M3 - Review article
C2 - 23128497
AN - SCOPUS:84871630327
SN - 0268-4705
VL - 28
SP - 63
EP - 71
JO - Current opinion in cardiology
JF - Current opinion in cardiology
IS - 1
ER -