Identification of the pathogenic effects of missense variants causing PRKAG2 cardiomyopathy.

BACKGROUND: Pathogenic missense variants in PRKAG2, the gene for the gamma 2 regulatory subunit of adenosine monophosphate-activated protein kinase (AMPK), cause severe progressive cardiac disease and sudden cardiac death, named PRKAG2 cardiomyopathy. In our previous study, we reported a E506K variant in the PRKAG2 gene that was associated with this disease. This study aimed to functionally characterize the three missense variants (E506K, E506Q, and R531G) of PRKAG2 and determine the possible effects on AMPK activity. METHODS: The proband was clinically monitored for eight years. To investigate the functional effects of three missense variants of PRKAG2, in vitro mutagenesis experiments using HEK293 cells with wild and mutant transcripts and proteins were comparatively analyzed using quantitative RT-PCR, immunofluorescence staining, and enzyme-linked immunosorbent assay. RESULTS: In the long-term follow-up, the proband was deceased due to progressive heart failure. In the in vitro experimental studies, PRKAG2 was overexpressed after 48 h of transfection in three mutated cells, after which the expression levels of PRKAG2 were regressed to the level of wild-type cells in 3-weeks stably transformed cells, except for the cells with E506K variant. E506K, E506Q, and R531G variants had caused a reduction in the AMPK activity and resulted in the formation of cytoplasmic glycogen deposits. CONCLUSION: Three missense variants that alter AMPK activity affect a residue in the CBS4 domain associated with ATP/AMP-binding. Detailed information on the influence of PRKAG2 pathogenic variants on AMPK activity would be helpful to improve the treatment and management of patients with metabolic cardiomyopathy.

Management of spontaneous pneumothorax in patients with COVID-19.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pneumonia may cause cystic features of lung parenchyma which can resolve or progress to larger blebs. Pneumothorax was more likely in patients with neutrophilia, severe lung injury and a prolonged clinical course. The timely diagnosis and management will reduce COVID-19-associated morbidity and mortality. METHODS: We present 11 cases of spontaneous pneumothorax managed with chest tube thoracostomy or high-dose oxygen therapy. Isolated spontaneous pneumothorax was detected in all cases. RESULTS: Eight cases were male and 3 cases were female. There were bilateral ground-glass opacities or pulmonary infiltrates in the parenchyma of the 10 cases. We detected neutrophilia, lymphopaenia and increased C-reactive protein, Ferritin, lactate dehydrogenase, D-Dimer, interleukin-6 levels in almost all cases. Chest tube thoracostomy was sufficient to treat pneumothorax in our 9 of case. In 2 cases, pneumothorax healed with high-dose oxygen therapy. Favipiravir and antibiotic treatment were given to different 10 patients. In our institution, all patients with COVID-19 infection were placed on prophylactic or therapeutic anticoagulation, unless contraindicated. The treatments of patients diagnosed with secondary spontaneous pneumothorax during the pandemic period and those diagnosed with secondary spontaneous pneumothorax in the previous 3 years were compared with the durations of tube thoracostomy performed in both groups. CONCLUSIONS: The increased number of cases of pneumothorax suggests that pneumothorax may be a complication of COVID-19 infection. During medical treatment of COVID-19, pneumothorax may be the only reason for hospitalization. Although tube thoracostomy is a sufficient treatment option in most cases, clinicians should be aware of the difficulties that may arise in diagnosis and treatment.

TaqI, FokI, and ApaI Polymorphisms in the Vitamin D Receptor in Behçet's Disease in Turkish Population.

Objectives. In our study we aimed to determine VDR gene polymorphisms in patients with Behçet's disease (BD) and neuro-Behçet's disease (NBD) in Turkish population. Methods. PBL obtained from 37 patients with BD, 21 patients with NB, and 30 healthy controls were investigated. Genomic DNA was extracted from whole blood using the QIAamp Blood Kit. VDR ApaI (rs7975232), VDR FokI (rs2228570), and VDR TaqI (rs731236) genotyping was performed by real-time polymerase chain reaction with SimpleProbe melting-curve analysis. Results. The allelic and genotype distributions of FokI and TaqI polymorphisms were not different among Behçet's disease, neuro-Behçet's disease, and control subjects in Turkish population (p > 0.05). Only the frequency of ApaI A allele in control is higher than that in BD (60% versus 38.5%), and the p value is 0.014, but the power is not enough to conclude that ApaI A allele is protective in BD in our study. Taken together, we found no significant differences between the BD, NBD, and control groups regarding the distribution of ApaI, TaqI, and FokI genotype and alleles frequencies. Conclusions. Future studies with larger patients' numbers may show differences between VDR polymorphisms and Behçet's disease.