A severe form of infantile cardiomyopathy (CM) has been linked to ELAC2 gene mutations. ELAC2 is a highly conserved human gene. It encodes RNaseZL endoribonuclease that plays an essential role in the production of mature tRNAs. To establish a causal connection between ELAC2 variants and CM, here we use a model organism Drosophila melanogaster, which carries ELAC2 homolog - dRNaseZ. Even though dRNaseZ and ELAC2 have diverged in some of their biological functions, our study demonstrates the utility of the fly model to study the mechanism of ELAC2 related pathology. We established transgenic lines harboring dRNaseZ with CM-linked mutations in the background of endogenous dRNaseZ knockout. Importantly, we found that the phenotype of these flies is consistent with pathological features in human patients. Specifically, expression of CM-linked variants in flies causes heart hypertrophy and leads to reduction in cardiac contractility associated with a rare form of CM. This study provides first experimental evidence for the pathogenicity of CM-causing mutations in the ELAC2 protein and lay the foundation to improve our understanding and diagnosis of this rare infantile disease.

No abstract

Cardiomyopathy (CM) is a group of diseases distinguished by morphological and functional abnormalities in the myocardium. It is etiologically heterogeneous and may develop via cell autonomous and/or non-autonomous mechanisms. One of the most severe forms of CM has been linked to the deficiency of the ubiquitously expressed RNase Z endoribonuclease. RNase Z cleaves off the 3’-trailer of both nuclear and mitochondrial primary tRNA (pre-tRNA) transcripts. Cells mutant for RNase Z accumulate unprocessed pre-tRNA molecules. Patients carrying RNase Z variants with reduced enzymatic activity display a plethora of symptoms including muscular hypotonia, microcephaly and severe heart hypertrophy; still, they die primarily due to acute heart decompensation. Determining whether the underlying mechanism of heart malfunction is cell autonomous or not will provide an opportunity to develop novel strategies of more efficient treatments for these patients. In this study, we used CRISPR-TRiM technology to create Drosophila models that carry cardiomyopathy-linked alleles of RNase Z only in the cardiomyocytes. We found that this modification is sufficient for flies to develop heart hypertrophy and systolic dysfunction. These observations support the idea that the RNase Z linked CM is driven by cell autonomous mechanisms.

No abstract

Aim. To assess the changes in cardiology diagnostics scope in the Russian Federation during the coronavirus disease 2019 (COVID-19) pandemic.Material and methods. In an online survey organized by the Division of Human Health of the International Atomic Energy Agency (IAEA), including questions about changes in the workflow of diagnostic laboratories and the scope of cardiac diagnostics from March 2019 (pre-pandemic) to April 2020 (first wave of the pandemic) and April 2021 (recovery stage), 15 Russian medical centers from 5 cities took part.Results. The decrease in the diagnostics scope by April 2020 by 59,3% compared to March 2019, by April 2021, stopped and was replaced by growth (+7,1%, the recovery rate, 112,1%). The greatest increase was in routine examinations, such as echocardiography (+11,6%), stress echocardiography (+18,7%), stress single photon emission computed tomography (+9,7%), and to a lesser extent resting computed tomography angiography (+7,0%) and magnetic resonance imaging (+6,6%). The performance of stress electrocardiography, stress magnetic resonance imaging and positron emission tomography for the diagnosis of endocarditis in April 2021 compared to March 2019 decreased by 10,3%, 63,2% and 62,5%, respectively.Conclusion. Due to the resumption of patient admissions for cardiac examinations during the ongoing COVID-19 pandemic, with the anti-epidemic measures taken and certain changes in the workflow, there has been a recovery in the diagnostics scope in most of the included centers.