BibTex format

author = {Cartwright, JH and Aziz, Q and Harmer, SC and Thayyil, S and Tinker, A and Munroe, PB},
doi = {hmg/ddz198},
journal = {Human Molecular Genetics},
pages = {1797--1807},
title = {Genetic variants in TRPM7 associated with unexplained stillbirth modify ion channel function},
url = {},
volume = {29},
year = {2020}

RIS format (EndNote, RefMan)

AB - INTRODUCTION: Stillbirth is the loss of a foetus after 22 weeks of gestation, of which almost half go completely unexplained despite post-mortem. We recently sequenced 35 arrhythmia-associated genes from 70 unexplained stillbirth cases. Our hypothesis was that deleterious mutations in channelopathy genes may have a functional effect in utero that may be pro-arrhythmic in the developing foetus. We observed four heterozygous, nonsynonymous variants in TRPM7, a ubiquitously expressed ion channel known to regulate cardiac development and repolarisation in mice. METHODS: We used site-directed mutagenesis and single-cell patch-clamp to analyse the functional effect of the four stillbirth mutants on TRPM7 ion channel function in heterologous cells. We also used cardiomyocytes derived from human pluripotent stem cells to model the contribution of TRPM7 to action potential morphology. RESULTS: Our results show that two TRPM7 variants, p.G179V and p.T860M lead to a marked reduction in ion channel conductance. This observation was underpinned by a lack of measurable TRPM7 protein expression, which in the case of p.T860M was due to rapid proteasomal degradation. We also report that human hiPSC-derived cardiomyocytes possess measurable TRPM7 currents, however siRNA knockdown did not directly affect action potential morphology. CONCLUSION: TRPM7 variants found in the unexplained stillbirth population adversely affect ion channel function and this may precipitate fatal arrhythmia in utero.
AU - Cartwright,JH
AU - Aziz,Q
AU - Harmer,SC
AU - Thayyil,S
AU - Tinker,A
AU - Munroe,PB
DO - hmg/ddz198
EP - 1807
PY - 2020///
SN - 0964-6906
SP - 1797
TI - Genetic variants in TRPM7 associated with unexplained stillbirth modify ion channel function
T2 - Human Molecular Genetics
UR -
UR -
UR -
UR -
VL - 29
ER -