Abstract. Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia responsible for substantial morbidity and significantly increased mortality rates. A growing body of evidence documents the important role of genetic defects in the pathogenesis of AF. However, AF is a heterogeneous disease and the genetic determinants for AF in an overwhelming majority of patients remain unknown. In the present study, a cohort of 100 unrelated patients with lone AF and a total of 200 unrelated, ethnically matched healthy individuals used as controls, were recruited. The whole coding exons and splice junctions of the pituitary homeobox 2c (PITX2c) gene, which encodes a paired-like homeobox transcription factor required for normal cardiovascular morphogenesis, were sequenced in the 100 patients and 200 control subjects. The causative potential of the identified mutation of PITX2c was predicted by MutationTaster and PolyPhen-2. The functional characteristics of the PITX2c mutation were assayed using a dual-luciferase reporter assay system. Based on the results, a novel heterozygous PITX2c mutation (p.T97A) was identified in a patient with AF. The missense mutation was absent in the 400 reference chromosomes and was automatically predicted to be disease-causing. Multiple alignments of PITX2c protein sequences across species revealed that the altered amino acid was completely conserved evolutionarily. Functional analysis demonstrated that the mutant PITX2c protein was associated with significantly decreased transcriptional activity when compared with its wild-type counterpart. The findings of the present study firstly link the PITX2c loss-of-function mutation to lone AF, and provide novel insight into the molecular mechanisms underlying AF, suggesting the potential implications for the early prophylaxis and allele-specific therapy of this common type of arrhythmia.

No abstract

No abstract

Background. We aimed to investigate the symptoms of the dry eye disease (DED) of hospitalized patients with coronavirus disease 2019 (COVID-19). Methods. This cross-sectional, observational study analysis included 91 hospitalized patients with confirmed COVID-19 in Wuhan, China. The Ocular Surface Disease Index (OSDI) and the five-item Dry Eye Questionnaire (DEQ-5) were used to assess the severity of DED symptoms in the patients, and the analysis of variance was used to determine the factors associated with DED. Results. A total of 42 patients consented to complete the investigation (response rate 46.15%). There were 26 (61.90%) patients who were diagnosed with DED symptoms by OSDI, and there were 28 (66.67%) patients with DED symptoms who were diagnosed by DEQ-5 score. For the biochemical tests, the patients with DED symptoms had lower aspartate aminotransferase (AST) levels compared to those with no DED symptoms (20.86 vs. 42.14, p = 0.04 ). Further analysis showed that a previous history of cardiac or stroke disease ( p = 0.02 ) and typical symptoms of muscle soreness ( p = 0.03 ) were significantly different among the four DED symptoms groups on the basis of OSDI scores. The contributing factors of OSDI were mainly focused on visual function and environmental triggers. Conclusion. The incidence of DED symptoms is higher in hospitalized patients with COVID-19. The serum AST levels, history of cardiac or stroke disease, and the typical symptoms of muscle soreness may be the main impact factors on DED symptoms. We also need to pay more attention to the visual function and environmental triggers of hospitalized patients with COVID-19.

No abstract