The 4q deletion syndrome shows a broad spectrum of clinical manifestations consisting of key features comprising growth failure, developmental delay, craniofacial dysmorphism, digital anomalies, and cardiac and skeletal defects. We have identified a de novo interstitial distal deletion in a 9 month-old girl with growth failure, developmental delay, ventricular septum defect in the subaortic region, patent foramen ovale and patent ductus arteriosus, vascular malformation of the lung, dysgenesis of the corpus callosum and craniofacial dysmorphism using array-comparative genomic hybridization. This de novo deletion is located at 4q28.3-31.23 (136,127,048 - 150,690,325), its size is 14.56 Mb, and contains 8 relevant genes (PCDH18, SETD7, ELMOD2, IL15, GAB1, HHIP, SMAD1, NR3C2) with possible contributions to the phenotype. Among other functions, a role in lung morphogenesis and tubulogenesis can be attributed to the deleted genes in our patient, which may explain the unique feature of vascular malformation of the lung leading to pulmonary hypertension. With the detailed molecular characterization of our case with 4q- syndrome we hope to contribute to the elucidation of the genetic spectrum of this disorder.

Background: Approximately fifteen percent of patients with tuberous sclerosis complex (TSC) phenotype do not have any genetic disease-causing mutations which could be responsible for the development of TSC. The lack of a proper diagnosis significantly affects the quality of life for these patients and their families. Methods: The aim of our study was to use Whole Exome Sequencing (WES) in order to identify the genes responsible for the phenotype of nine patients with clinical signs of TSC, but without confirmed tuberous sclerosis complex 1/ tuberous sclerosis complex 2 (TSC1/TSC2) mutations using routine molecular genetic diagnostic tools. Results: We found previously overlooked heterozygous nonsense mutations in TSC1, and a heterozygous intronic variant in TSC2. In one patient, two heterozygous missense variants were found in polycystic kidney and hepatic disease 1 (PKHD1), confirming polycystic kidney disease type 4. A heterozygous missense mutation in solute carrier family 12 member 5 (SLC12A5) was found in one patient, which is linked to cause susceptibility to idiopathic generalized epilepsy type 14. Heterozygous nonsense variant ring finger protein 213 (RNF213) was identified in one patient, which is associated with susceptibility to Moyamoya disease type 2. In the remaining three patients WES could not reveal any variants clinically relevant to the described phenotypes. Conclusion: Patients without appropriate diagnosis due to the lack of sensitivity of the currently used routine diagnostic methods can significantly profit from the wider application of next generation sequencing technologies in order to identify genes and variants responsible for their symptoms.

Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations, the role of nutrients, vitamins, and, in general, the foodborne-associated background, as part of the events ultimately leading to chromosome nondisjunction, has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes. The possible association of DS development with maternal gut microbiota should therefore require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa; and hence, we might find associations between the use of the different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N = 30). By utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997–2020) and the estimated prevalence of people living with DS for the year 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.

Background/Objectives: The Seklers are a Hungarian-speaking regional population in Transylvania, Romania, with a long and complex history, yet comprehensive genome-wide studies remain limited. Our aim was to characterize the genetic background of multiple Sekler communities using high-density autosomal data and to place them in a broader Central and Eastern European context. Methods: Here we analyzed genome-wide autosomal SNP data obtained from 17 Sekler groups. Allele frequency- and haplotype-based approaches were applied to assess overall genetic structure, ancestry patterns, recent shared ancestry, and signals of demographic history. Results: Analyses based on overall allele-frequency patterns showed that Sekler groups fit into a single, coherent genetic cluster shared with Hungarians. No major differences were detected among the Sekler communities at this broader genomic level, and their genetic profiles were largely indistinguishable from one another. Using haplotype-based methods, most Sekler groups again formed a compact cluster. However, two villages, Deményháza and Nyárádszentimre, showed clear signs of increased within-group relatedness and subtle separation. These patterns might indicate that both communities experienced stronger local drift and reduced effective population size, while other Sekler groups showed no comparable deviation from the general regional pattern. Conclusions: Although a small number of villages display modest signs of localized demographic drift, our results support that the Seklers represent a regionally distinct and internally cohesive population, whose genetic structure is shaped mainly by common historical and linguistic ties, with minor village-level variation, forming a uniform part of the Hungarian-speaking population of the East-Central European region.