Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders

\ua9 The Author(s) 2024. Background: Neurodevelopmental disorders (NDDs) and/or associated multiple congenital abnormalities (MCAs) represent a genetically heterogeneous group of conditions with an adverse prognosis for the quality of intellectual and social abilities and common daily functioning. The rapid development of exome sequencing (ES) techniques, together with trio-based analysis, nowadays leads to up to 50% diagnostic yield. Therefore, it is considered as the state-of-the-art approach in these diagnoses. Results: In our study, we present the results of ES in a cohort of 85 families with 90 children with severe NDDs and MCAs. The interconnection of the in-house bioinformatic pipeline and a unique algorithm for variant prioritization resulted in a diagnostic yield of up to 48.9% (44/90), including rare and novel causative variants (41/90) and intragenic copy-number variations (CNVs) (3/90). Of the total number of 47 causative variants, 53.2% (25/47) were novel, highlighting the clinical benefit of ES for unexplained NDDs. Moreover, trio-based ES was verified as a reliable tool for the detection of rare CNVs, ranging from intragenic exon deletions (GRIN2A, ZC4H2 genes) to a 6-Mb duplication. The functional analysis using PANTHER Gene Ontology confirmed the involvement of genes with causative variants in a wide spectrum of developmental processes and molecular pathways, which form essential structural and functional components of the central nervous system. Conclusion: Taken together, we present one of the first ES studies of this scale from the central European region. Based on the high diagnostic yield for paediatric NDDs in this study, 48.9%, we confirm trio-based ES as an effective and reliable first-tier diagnostic test in the genetic evaluation of children with NDDs

7th meeting of the global arthritis research network

Last October, the 7th meeting of the Global Arthritis Research Network was held in Zurich, Switzerland. European and American experts who have made major recent contributions to molecular biology got together to provide insights into novel technologies and approaches useful for biomedical research, especially for research on arthritis and related conditions

Vaspin and omentin: new adipokines differentially regulated at the site of inflammation in rheumatoid arthritis

Scientific interest in adipose tissue-derived peptides has increased dramatically in recent years (1). Several mediators known as adipo(cyto)kines were first associated with the pathophysiology of obesity-related complications; however a significant role for adipokines such as leptin, adiponectin, resistin and visfatin in regulating immune responses and inflammation has recently been discovered (1, 2). Several reports (3-6) have already demonstrated association of these adipokines with the severity of rheumatoid arthritis (RA). Vaspin, a member of the serine protease inhibitor family, and omentin (also known as intelectin) were recently identified in adipose tissue (7, 8). Vaspin is an adipokine with insulin-sensitizing effects that has been suggested to be a compensatory mediator for abrogating obesity and its inflammatory complications (7). Expression of the omentin gene was demonstrated in omental adipose tissue of patients with Crohn's disease, suggesting that it may be implicated in chronic inflammatory diseases (8). The aim of the present report was to compare local concentrations of vaspin and omentin in synovial fluid of RA patients with those in osteoarthritis (OA) patients and to characterize their potential association with the severity of the disease. Synovial fluid was obtained during therapeutic arthrocentesis from 33 patients with RA and 33 patients with knee OA. The disease activity of RA patients was assessed by DAS28. C-reactive protein (CRP), IgM-rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) were routinely analyzed from peripheral blood obtained at the time of arthrocentesis. Characteristics of the patients are given in Table 1. Vaspin (AdipoGen Inc. Korea) and omentin (Apotech Corporation) were analyzed in synovial fluid by ELISA assays. Ethical approval was obtained from the local Ethics Committee and all patients provided informed consent. Statistical analysis was performed using GraphPad Prism 5.0 software. To meet a normal distribution, vaspin and omentin concentrations were naturaly logarithmically (log)-transformed. Differences between two independent parameters were determined by Kruskal-Wallis or T-test. The Spearman test was used for correlation of parameters. As shown in figure 1, the mean (SD) levels of vaspin were significantly higher in the synovial fluid of RA patients than in OA patients (-2.439+/-1.226 vs. -3.366+/-1.318 (log) pg/ml; p=0.003), but interestingly the levels of omentin were significantly lower in the synovial fluid of RA patients compared to OA patients (1.491+/-0.948 vs. 1.964+/-0.902 (log) ng/ml; p=0.045). After log-transformation, synovial fluid vaspin, but not omentin, had a tendency to correlate with DAS28 (r=0.320, p=0.070) in RA patients. However, neither vaspin nor omentin correlated with serum CRP or leukocyte counts in synovial fluid. In addition, levels of synovial fluid omentin, but not vaspin, significantly correlated with serum ACPA (r=0.398, p=0.029) and IgM-RF (r=0.592, p<0.001). The levels of synovial fluid vaspin and omentin were not affected by body mass index (BMI) or age of the patients. The mean concentration of synovial fluid vaspin, but not omentin, was twice as high in female as in male patients, but possibly due to the low number of male patients in this study, it failed to reach statistical significance. Our data shows different levels of the new adipokines vaspin and omentin at the site of local inflammation. We demonstrate here for the first time elevated levels of vaspin and reduced levels of omentin in synovial fluid of patients with RA compared with those with OA

NiâNbâO catalysts for ethane oxidative dehydrogenation

RAFFINAGE+JMI:SLONon