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22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder with an extremely broad phenotypic spectrum. The aim of our study was to investigate how often the additional variants in the genome can affect clinical variation among patients with the recurrent deletion. To examine the presence of additional variants affecting the phenotype, we performed microarray in 82 prenatal and 77 postnatal cases and performed exome sequencing in 86 postnatal patients with 22q11.2DS. Within those 159 patients where array was performed, 5 pathogenic and 5 likely pathogenic CNVs were identified outside of the 22q11.2 region. This indicates that in 6.3% cases, additional CNVs most likely contribute to the clinical presentation. Additionally, exome sequencing in 86 patients revealed 3 pathogenic (3.49%) and 5 likely pathogenic (5.81%) SNVs and small CNV. These results show that the extension of diagnostics with genome-wide methods can reveal other clinically relevant changes in patients with 22q11 deletion syndrome.

The most common form of inherited lipid disorders is familial hypercholesterolemia (FH). It is characterized primarily by high concentrations of the clinical triad of low-density lipoprotein cholesterol, tendon xanthomas and premature CVD. The well-known genetic background are mutations in LDLR, APOB and PCSK9 gene. Causative mutations can be found in 60–80% of definite FH patients and 20–30% of those with possible FH. Their occurrence could be attributed to the activity of minor candidate genes, whose causal mechanism has not been fully discovered. The aim of the conducted study was to identify disease-causing mutations in FH-related and candidate genes in pediatric patients from Poland using next generation sequencing (NGS). An NGS custom panel was designed to cover 21 causative and candidate genes linked to primary dyslipidemia. Recruitment was performed using Simon Broome diagnostic criteria. Targeted next generation sequencing was performed on a MiniSeq sequencer (Illumina, San Diego, CA, USA) using a 2 × 150 bp paired-end read module. Sequencing data analysis revealed pathogenic and possibly pathogenic variants in 33 out of 57 studied children. The affected genes were LDLR, APOB, ABCG5 and LPL. A novel pathogenic 7bp frameshift deletion c.373_379delCAGTTCG in the exon 4 of the LDLR gene was found. Our findings are the first to identify the c.373_379delCAGTTCG mutation in the LDLR gene. Furthermore, the double heterozygous carrier of frameshift insertion c.2416dupG in the LDLR gene and missense variant c.10708C>T in the APOB gene was identified. The c.2416dupG variant was defined as pathogenic, as confirmed by its cosegregation with hypercholesterolemia in the proband’s family. Although the APOB c.10708C>T variant was previously detected in hypercholesterolemic patients, our data seem to demonstrate no clinical impact. Two missense variants in the LPL gene associated with elevated triglyceride plasma level (c.106G>A and c.953A>G) were also identified. The custom NGS panel proved to be an effective research tool for identifying new causative aberrations in a genetically heterogeneous disease as familial hypercholesterolemia (FH). Our findings expand the spectrum of variants associated with the FH loci and will be of value in genetic counseling among patients with the disease.

In EN 13670:2009 standard: Execution of concrete structures there are general rules of moisture curing of concrete in structures. In the standard 4 classes of concrete curing are described. Determination of curing class depends on required level of compressive strength immediately after curing (percentage of required characteristic strength after 28 days). Time of curing depends on rate of strength development and concrete surface temperature. In the standard there is a lack of information about influence of curing class on concrete durability characteristics. The main condition to obtain durable concrete is proper curing regime. Not cured on improperly cured concrete has weakened surface layer. Extremely faults in curing process could lead to defects visible on the concrete surface. More often defects are latent inside the concrete and could be revealed during exploitation, leading to durability reduction. The main effect is increase of surface layer porosity (reinforcement cover) and decrease of its protective properties and tightness. Consequently worsening of mechanical properties could be observed as well as water-tightness, frost resistance, chemical aggression resistance, carbonation resistance and diffusivity of chloride. The analysis shown in the paper are the result of 3-yers long investigation conducted by authors, which main goal was to determine appropriateness and way to include durability requirements in designing of curing class according to EN 13670:2009. Thawing-freezing resistance, scaling with salts resistance, depth of water penetration under pressure and absorptivity were adopted as the basic durability factors. Concretes with different cement types, different rate of compressive strength development, air-entrained and non-air-entrained were tested. Time of curing was differentiated in the range of classes 1,3,4 following standard EN 13670:2009 requirements. Practical conclusions were formulated which allows to consider durability presumptions in technological requirements contained in concrete works specifications.