Long-QT founder variant T309I-Kv7.1 with dominant negative pattern may predispose delayed afterdepolarizations under ß-adrenergic stimulation.

The variant c.926C > T (p.T309I) in KCNQ1 gene was identified in 10 putatively unrelated Czech families with long QT syndrome (LQTS). Mutation carriers (24 heterozygous individuals) were more symptomatic compared to their non-affected relatives (17 individuals). The carriers showed a mild LQTS phenotype including a longer QTc interval at rest (466 ± 24 ms vs. 418 ± 20 ms) and after exercise (508 ± 32 ms vs. 417 ± 24 ms), 4 syncopes and 2 aborted cardiac arrests. The same haplotype associated with the c.926C > T variant was identified in all probands. Using the whole cell patch clamp technique and confocal microscopy, a complete loss of channel function was revealed in the homozygous setting, caused by an impaired channel trafficking. Dominant negativity with preserved reactivity to ß-adrenergic stimulation was apparent in the heterozygous setting. In simulations on a human ventricular cell model, the dysfunction resulted in delayed afterdepolarizations (DADs) and premature action potentials under ß-adrenergic stimulation that could be prevented by a slight inhibition of calcium current. We conclude that the KCNQ1 variant c.926C > T is the first identified LQTS-related founder mutation in Central Europe. The dominant negative channel dysfunction may lead to DADs under ß-adrenergic stimulation. Inhibition of calcium current could be possible therapeutic strategy in LQTS1 patients refractory to ß-blocker therapy.

Out-of-Hospital Cardiac Arrest Due to Ventricular Fibrillation in a 5-Year-Old Pediatric Patient.

Out-of-hospital cardiac arrest in pediatric population is rare and predominantly has respiratory aetiology. Authors present the relatively unique case of out-of hospital cardiac arrest in 5-years old pediatric patient due to ventricular fibrillation (VF) as the initial rhythm during the advanced life support. The patient was resuscitated by his parents and the initial rhythm was VF. After defibrillation the patient was admitted to the pediatric intensive care were another two episodes of VF was detected and treated. After standard postresuscitation care, patient was weaned from sedation and extubated with good neurologic outcome. Genetic screening of the 7 genes associated with cardiac channelopathies (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, RYR2, CASQ2) found mutation in gene KCHN2 and gene SCN5A, that were according to actual data considered benign. This case highlights the need for automated external defibrillator implementation in basic life support also in pediatric population and possible role of genetic predisposition in emergence of fibrillation.

Bioaccumulation of heavy metals, metalloids, and chlorine in ectomycorrhizae from smelter-polluted area.

Ectomycorrhizal (ECM) fungi contribute to the survival of host trees on metal-rich soils by reducing the transfer of toxic metals into roots. However, little is known about the ability of ECM fungi to accumulate elements in ectomycorrhizae (ECMs). Here we report Ag, As, Cd, Cl, Cu, Sb, V, and Zn contents in wild-grown Norway spruce ECMs collected in a smelter-polluted area at Lhota near Príbram, Czech Republic. The ECMs data were compared with the element concentrations determined in the corresponding non-mycorrhizal fine roots, soils, and soil extracts. Bioaccumulation factors were calculated to differentiate the element accumulation ability of ECMs inhabited by different mycobionts, which were identified by ITS rDNA sequencing. Among the target elements, the highest contents were observed for Ag, Cl, Cd, and Zn; Imleria badia ECMs showed the highest capability to accumulate these elements. ECMs of Amanita muscaria, but not of other species, accumulated V. The analysis of the proportions of I. badia and A. muscaria mycelia in ECMs by using species-specific quantitative real-time PCR revealed variable extent of the colonization of roots, with median values close to 5% (w/w). Calculated Ag, Cd, Zn and Cl concentrations in the mycelium of I. badia ECMs were 1 680, 1 510, 2 670, and 37,100 mg kg-1 dry weight, respectively, indicating substantial element accumulation capacity of hyphae of this species in ECMs. Our data strengthen the idea of an active role of ECM fungi in soil-fungal-plant interactions in polluted environments.