BibTex format
@article{Munroe:2018:10.1161/CIRCGEN.117.001817,
author = {Munroe, PB and Addison, S and Abrams, DJ and Sebire, NJ and Cartwright, J and Donaldson, I and Cohen, MM and Mein, C and Tinker, A and Harmer, SC and Aziz, Q and Terry, A and Struebig, M and Warren, HR and Vadgama, B and Fowler, DJ and Peebles, D and Taylor, AM and Lally, PJ and Thayyil, S},
doi = {10.1161/CIRCGEN.117.001817},
journal = {Circulation: Cardiovascular Genetics},
title = {Postmortem genetic testing for cardiac ion channelopathies in stillbirths},
url = {http://dx.doi.org/10.1161/CIRCGEN.117.001817},
volume = {11},
year = {2018}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BackgroundAlthough stillbirth is a significant health problem worldwide, the definitive cause of death remains elusive in many cases, despite detailed autopsy. In this study of partly explained and unexplained stillbirths, we used next-generation sequencing to examine an extended panel of 35 candidate genes known to be associated with ion channel disorders and sudden cardiac death.Methods and ResultsWe examined tissue from 242 stillbirths (≥22 weeks), including those where no definite cause of death could be confirmed after a full autopsy. We obtained high-quality DNA from 70 cases, which were then sequenced for a custom panel of 35 genes, 12 for inherited long- and short-QT syndrome genes (LQT1-LQT12 and SQT1-3), and 23 additional candidate genes derived from genome-wide association studies. We examined the functional significance of a selected variant by patch-clamp electrophysiological recording. No predicted damaging variants were identified in KCNQ1 (LQT1) or KCNH2 (LQT2). A rare putative pathogenic variant was found in KCNJ2(LQT7) in 1 case, and several novel variants of uncertain significance were observed. The KCNJ2 variant (p. R40Q), when assessed by whole-cell patch clamp, affected the function of the channel. There was no significant evidence of enrichment of rare predicted damaging variants within any of the candidate genes.ConclusionsAlthough a causative link is unclear, 1 putative pathogenic and variants of uncertain significance variant resulting in cardiac channelopathies was identified in some cases of otherwise unexplained stillbirth, and these variants may have a role in fetal demise.
AU - Munroe,PB
AU - Addison,S
AU - Abrams,DJ
AU - Sebire,NJ
AU - Cartwright,J
AU - Donaldson,I
AU - Cohen,MM
AU - Mein,C
AU - Tinker,A
AU - Harmer,SC
AU - Aziz,Q
AU - Terry,A
AU - Struebig,M
AU - Warren,HR
AU - Vadgama,B
AU - Fowler,DJ
AU - Peebles,D
AU - Taylor,AM
AU - Lally,PJ
AU - Thayyil,S
DO - 10.1161/CIRCGEN.117.001817
PY - 2018///
SN - 1942-325X
TI - Postmortem genetic testing for cardiac ion channelopathies in stillbirths
T2 - Circulation: Cardiovascular Genetics
UR - http://dx.doi.org/10.1161/CIRCGEN.117.001817
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000428988100005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/63477
VL - 11
ER -
