{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:08:39Z","timestamp":1790723319900,"version":"4.1.0"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,9,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Recurrent pregnancy loss affects 1% to 2% of couples attempting childbirth. A large fraction of all cases remains idiopathic, which warrants research into monogenic causes of this distressing disorder.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We investigated a nonconsanguineous Estonian family who had experienced 5 live births, intersected by 3 early pregnancy losses, and 6 fetal deaths, 3 of which occurred during the second trimester. No fetal malformations were described at the autopsies performed in 3 of 6 cases of fetal death. Parental and fetal chromosomal abnormalities (including submicroscopic) and maternal risk factors were excluded. Material for genetic testing was available from 4 miscarried cases (gestational weeks 11, 14, 17, and 18). Exome sequencing in 3 pregnancy losses and the mother identified no rare variants explicitly shared by the miscarried conceptuses. However, the mother and 2 pregnancy losses carried a heterozygous nonsynonymous variant, resulting in p.Val173Asp (\n              <jats:italic>rs199472695<\/jats:italic>\n              ) in the ion channel gene\n              <jats:italic>KCNQ1<\/jats:italic>\n              . It is expressed not only in heart, where mutations cause type 1 long\u2010QT syndrome, but also in other tissues, including uterus. The p.Val173Asp variant has been previously identified in a patient with type 1 long\u2010QT syndrome, but not reported in the Genome Aggregation Database. With heterologous expression in CHO cells, our in vitro electrophysiologic studies indicated that the mutant slowly activating voltage\u2010gated K+ channel (\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Ks<\/jats:sub>\n              ) is dysfunctional. It showed reduced total activating and deactivating currents (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01), with dramatically positive shift of voltage dependence of activation by \u224810 mV (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The current study uncovered concealed maternal type 1 long\u2010QT syndrome as a potential novel cause behind recurrent fetal loss.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.021236","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T18:22:32Z","timestamp":1629138152000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Recurrent Pregnancy Loss and Concealed Long\u2010QT 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