TY - JOUR
T1 - The genetic architecture of long QT syndrome: A critical reappraisal
AU - Giudicessi, John R.
AU - Wilde, Arthur A. M.
AU - Ackerman, Michael J.
PY - 2018
Y1 - 2018
N2 - Collectively, the completion of the Human Genome Project and subsequent development of high-throughput next-generation sequencing methodologies have revolutionized genomic research. However, the rapid sequencing and analysis of thousands upon thousands of human exomes and genomes has taught us that most genes, including those known to cause heritable cardiovascular disorders such as long QT syndrome, harbor an unexpected background rate of rare, and presumably innocuous, non-synonymous genetic variation. In this Review, we aim to reappraise the genetic architecture underlying both the acquired and congenital forms of long QT syndrome by examining how the clinical phenotype associated with and background genetic variation in long QT syndrome-susceptibility genes impacts the clinical validity of existing gene-disease associations and the variant classification and reporting strategies that serve as the foundation for diagnostic long QT syndrome genetic testing.
AB - Collectively, the completion of the Human Genome Project and subsequent development of high-throughput next-generation sequencing methodologies have revolutionized genomic research. However, the rapid sequencing and analysis of thousands upon thousands of human exomes and genomes has taught us that most genes, including those known to cause heritable cardiovascular disorders such as long QT syndrome, harbor an unexpected background rate of rare, and presumably innocuous, non-synonymous genetic variation. In this Review, we aim to reappraise the genetic architecture underlying both the acquired and congenital forms of long QT syndrome by examining how the clinical phenotype associated with and background genetic variation in long QT syndrome-susceptibility genes impacts the clinical validity of existing gene-disease associations and the variant classification and reporting strategies that serve as the foundation for diagnostic long QT syndrome genetic testing.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85045560566&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29661707
U2 - https://doi.org/10.1016/j.tcm.2018.03.003
DO - https://doi.org/10.1016/j.tcm.2018.03.003
M3 - Review article
C2 - 29661707
SN - 1050-1738
VL - 28
SP - 453
EP - 464
JO - Trends in cardiovascular medicine
JF - Trends in cardiovascular medicine
IS - 7
ER -