Open AccessIn vitro analyses of suspected arrhythmogenic thin filament variants as a cause of sudden cardiac death in infants
Author(s) -
Sanam Shafaattalab,
Alison Yueh Li,
Eric Lin,
Charles M. Stevens,
Laura Dewar,
Francis C. Lynn,
Shubhayan Sanatani,
Zachary Laksman,
Ryan D. Morin,
Filip Van Petegem,
Leif HoveMadsen,
D. Peter Tieleman,
Jonathan P. Davis,
Glen F. Tibbits
Publication year - 2019
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1819023116
Subject(s) - sudden infant death syndrome , in silico , sudden cardiac death , sudden death , biology , in vitro , gene , medicine , bioinformatics , genetics , cardiology , neuroscience , pediatrics
Significance A major aim of this study was to develop an experimental pipeline for the analysis and assessment of variants potentially causal in sudden cardiac death of infants (SCDI). TheTNNI R37C+/− variant in this study was reliably and reproducibly disruptive to the normal physiology, in contrast to that in isogenic controls, across a battery of in silico and in vitro assays. This strengthens the evidence of pathogenicity and implicates a neonatal gene paralog encoding a sarcomeric contractile protein as having likely contributed to SCDI through a proarrhythmic pathway. This platform has the potential to be applied broadly as part of a standardized and clinically relevant death investigation in cases of SCDI where novel variants are identified.
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