Genetic variants are tied to dysfunctional long QT syndrome-associated ion channels in vitro
WEDNESDAY, April 10 (HealthDay News) -- Missense mutations associated with long QT syndrome (LQTS) susceptibility may explain some cases of intrauterine fetal death, according to a study published April 10 in the Journal of the American Medical Association.
Lia Crotti, M.D., Ph.D., from the University of Pavia in Italy, and colleagues examined the spectrum and prevalence of mutations in the three most common LQTS susceptibility genes in a sample of 91 unexplained intrauterine fetal deaths. Controls included more than 1,300 ostensibly healthy individuals. High-performance liquid chromatography was used to perform mutational analyses of KCNQ1, KCNQ2, and SCN5A, and genomic DNA extracted from decedent tissue was sequenced.
The researchers found that in three intrauterine fetal deaths, three putative LQTS susceptibility missense mutations were identified (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2[1b], p.R25W). Two of these mutations correlated with loss-of-function consistent with in utero LQTS type 1 (p.A283T and p.R397W), and one exhibited loss-of-function consistent with in utero LQTS type 2 (p.R25W). Rare non-synonymous genetic variants in SCN5A were identified in five intrauterine deaths; these mutations conferred in vitro electrophysiological characteristics consistent with phenotypes that were possibly proarrhythmic.
"In this molecular genetic evaluation of 91 cases of intrauterine fetal death, missense mutations associated with LQTS susceptibility were discovered in three cases (3.3 percent), and overall, genetic variants leading to dysfunctional LQTS-associated ion channels in vitro were discovered in eight cases (8.8 percent)," the authors write. "This preliminary evidence provided by our present study suggests that LQTS may contribute to the pathogenesis of some intrauterine fetal deaths."
Several authors disclosed financial ties to the pharmaceutical industry.
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