Background: Array‐based genomic analysis is a gold standard for the detection of copy number variations (CNVs) as an important source of benign as well as pathogenic variations in humans. The introduction of chromosomal microarray (CMA) has led to a significant leap in diagnostics of genetically caused congenital malformations and neurodevelopmental disorders, with an average diagnostic yield of 15%. Here, we present our experience from a single laboratory perspective in four years’ postnatal clinical CMA application.Methods: DNA samples of 430 patients with congenital anomalies and/or neurodevelopmental disorders were analyzed by comparative genome hybridization using oligonucleotide‐based microarray platforms. Interpretation of detected CNVs was performed according to current guidelines. The detection rate (DR) of clinically significant findings (pathogenic/likely pathogenic CNVs) was calculated for the whole cohort and isolated or combined phenotypic categories.Results: A total of 140 non‐benign CNVs were detected in 113/430 patients (26.5%). In 70 patients at least one CNV was considered clinically significant thus reaching a diagnostic yield of 16.3%. The more complex the phenotype, including developmental delay/intellectual disability (DD/ID) as a prevailing feature, the higher the DR of clinically significant CNVs is obtained. Isolated congenital anomalies had the lowest, while the “dysmorphism plus” category had the highest diagnostic yield.Conclusion: In our study, CMA proved to be a very useful method in the diagnosis of genetically caused congenital anomalies and neurodevelopmental disorders. DD/ID and dysmorphism stand out as important phenotypic features that significantly increase the diagnostic yield of the analysis.

Galectin 3 plays a significant role in the development of chronic renal failure, particularly end-stage renal disease (ESRD). The aim of our study was to investigate the association between Gal-3 and biochemical parameters and primary disease in ESRD patients, by exploring the polymorphisms LGALS3 rs4644, rs4652, and rs11125. A total of 108 ESRD patients and 38 healthy controls were enrolled in the study. Genotyping of LGALS3 gene rs4644, rs4652, and rs11125 polymorphisms was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). By multivariate logistic regression analysis, we found that LGALS3 rs4644 CC and rs4652 AA genotypes were significantly associated with a higher risk for lower hemoglobin, higher level of parathyroid hormone, and also occurrence of diabetes mellitus and arterial hypertension. The CAA haplotype was significantly more common in patients with diabetes, low hemoglobin level, and normal PTH level. It has been observed as well that the ACT haplotype was more common in patients with low glomerular filtration, low PTH, and normal hemoglobin level. We found that the LGALS3 rs4644 and rs4652 gene polymorphism may be involved in the pathogenesis and appearance of complications in ESRD patients and thus could be considered a new genetic risk factor in this population.

Objectives: Inflammatory cytokines like tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6 can cause brain injury, slow recovery, and adverse effects (ADEs) in ischemic stroke (IS) patients treated with recombinant tissue plasminogen activator (rtPA). We explored the relationship between selected polymorphisms within TNF-alpha, IL-1 beta and IL-6 genes, and post-IS outcome and ADEs in patients treated with rtPA.Methods: One hundred and sixty-six patients with IS treated with rtPA were included in this study. The modified Rankin Scale (mRS) was used to assess functional recovery 3 months after IS likewise thrombolytic therapy efficacy. Patients were classified into groups with favorable (0-1) or poor recovery based on their mRS score at the ninetieth day post-IS. During hospitalization, ADEs following rtPA were monitored. TNF-alpha-308 G/A (rs1800629), IL-1 beta-511 G/A (rs16944), and IL-6-174 G/C (rs1800795) polymorphisms were genotyped using Real-Time PCR. SPSS software version 22.0 was used for statistical analyses.Results: Patients with the TNF-alpha-308 G/A GG genotype had a higher mean NIHSS value at admission (12.75 +/- 5.176) than those carrying A-allele (10.56 +/- 3.979;p = 0.016). Individuals with the CC genotype of the IL-6-174 G/C polymorphism had significantly lower NIHSS scores (8.79 +/- 5.053) than those with G-allele (12.06 +/- 6.562) 24 hours after rtPA (p = 0.050). Patients with the GG genotype of the IL-6-174 G/C polymorphism had a significantly poorer outcome (p = 0.024; OR = 2.339; 95%CI 1.121-4.880), while patients who were G-allele carriers of the Il-6-174 G/C polymorphism and had the AA genotype of the IL-1 beta-511 G/A polymorphism were statistically significantly more likely to experience hemorrhagic transformation (p = 0.046; OR = 2.7273; 95%CI 1.0414-7.1426).Conclusion: GG genotype of the IL-6-174 G/C polymorphism is associated with poor recovery after IS treated with rtPA therapy.

Introduction: Positive regulatory domain containing 16 (PRDM16) protein represents the key regulator of brown adipose tissue (BAT) development. It induces brown fat phenotype and represses white adipose tissue specific genes through the association with C-terminal binding co-repressor proteins...

Secondary peritonitis (SP) remains a major clinical challenge due to its high complication rates and it often results in sepsis and multi-organ dysfunction. This study investigated the association between four nitric oxide synthase (NOS) single-nucleotide polymorphisms (SNPs)—NOS3 c.-786T>C (rs2070744), NOS3 c.894G>T (rs1799983), NOS3 27 bp variable number tandem repeat (VNTR) (rs61722009), and NOS2 (rs2297518)—and sepsis-related complications in 202 patients with SP. Demographic and baseline clinical characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Mannheim Peritonitis Index, and complications (multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF), acute respiratory distress syndrome (ARDS), and sepsis) were analyzed for associations with the NOS gene variants. Haplotype analysis was also performed. No SNP showed an association with in-hospital mortality. However, the NOS3 c.-786T>C TT genotype was significantly associated with an increased risk of MOF (p = 0.008), and remained independently associated after multivariate adjustment (p_MOF = 0.006). The T4bG haplotype was significantly more frequent among patients with MODS (p = 0.026), MOF (p = 0.048), and sepsis (p = 0.018). These findings suggest that NOS gene variants, particularly NOS3 c.-786T>C and the T4bG haplotype, may potentially serve as biomarkers for risk stratification in critically ill patients.