No abstract

Familial hypercholesterolemia (FH) is one of the most common autosomal, dominantly inherited diseases affecting cholesterol metabolism, which, in the absence of treatment, leads to the development of cardiovascular complications. The disease is still underdiagnosed, even though an early diagnosis would be of great importance for the patient to receive proper treatment and to prevent further complications. No studies are available describing the genetic background of Hungarian FH patients. In this work, we present the clinical and molecular data of 44 unrelated individuals with suspected FH. Sequencing of five FH-causing genes (LDLR, APOB, PCSK9, LDLRAP1 and STAP1) has been performed by next-generation sequencing (NGS). In cases where a copy number variation (CNV) has been detected by NGS, confirmation by multiplex ligation-dependent probe amplification (MLPA) has also been performed. We identified 47 causal or potentially causal (including variants of uncertain significance) LDLR and APOB variants in 44 index patients. The most common variant in the APOB gene was the c.10580G>A p.(Arg3527Gln) missense alteration, this being in accordance with literature data. Several missense variants in the LDLR gene were detected in more than one index patient. LDLR variants in the Hungarian population largely overlap with variants detected in neighboring countries.

Ufmylation is a relatively newly discovered type of post-translational modification when the ubiquitin-fold modifier 1 (UFM1) protein is covalently attached to its target proteins in a three-step enzymatic reaction involving an E1 activating enzyme (UBA5), E2 conjugating enzyme (UFC1), and E3 ligase enzyme (UFL1). The process of ufmylation is essential for normal brain development and function in humans. Mutations in the UFM1 gene are associated with Hypomyelinating leukodystrophy type 14, presenting with global developmental delay, failure to thrive, progressive microcephaly, refractive epilepsy, and hypomyelination, with atrophy of the basal ganglia and cerebellum phenotypes. The c.-155_-153delTCA deletion in the promoter region of UFM1 is considered to be a founding mutation in the Roma population. Here we present four index patients with homozygous UFM1:c.-155_-153delTCA mutation detected by next-generation sequencing (whole genome/exome sequencing) or Sanger sequencing. This mutation may be more common in the Roma population than previously estimated, and the targeted testing of the UFM1:c.-155_-153delTCA mutation may have an indication in cases of hypomyelination and neurodegenerative clinical course in pediatric patients of Roma descent.

Introduction: Recent research findings support the assumption that the development of chronic diseases in adults is greatly influenced by the supply of nutrients in the uterus and the nutrition, nourishment of the early, toddler ages. Aim: The aim of the present study was to evaluate the nutritional habits of infants and toddlers aged 0–3 in Hungary, and to identify the most typical problems of their nutrition, to get to know and provide the necessary data for the modification and modernization of feeding/nutrition recommendations for infants and young children in Hungary. Method: The study was carried out with the professional coordination of the Hungarian Dietetic Association (MDOSZ) in the framework of industry research between June and August 2015, in the 0–3-year-old population, in the cities Budapest, Debrecen, Győr, Szeged and Pécs. The survey was conducted with anthropometric measurements and validated by three-day dietary log templates. Results: 18.6% of infants aged 4 to 12 months (n = 220) had values below 10th percentile, 10% were between 85–97th percentiles and 3% were above 97th percentile. 15% of children aged 12–24 months (n = 227) had a body mass index (BMI) below 10th percentile (underweight), 14% were between 85–97th percentile (overweight) and 2.6% had BMI over the 97th percentile (obese). 70% of 25–36-month-old children (n = 184) had normal BMI, 4% were overweight, 2% obese, 24% underweight. Based on the Hungarian reference value, 10.9% of the 4–12-month-old children, 20% of the 1–2-year-olds, 47% of the 2–3-year-olds were in high protein intake group. However, compared to the 2013’s reference values of the EFSA (European Food Safety Authority) recommendation, 100% of the children belong to the high protein intake group in all age groups. Conclusion: Although the EFSA recommendation – based on the WHO/FAO/UNU macro- and micronutrient intake values in 2007 – defines the recommended intake quantities, the results in the sample did not support its overall reliability. Orv Hetil. 2019; 160(50): 1990–1998.

Our aim was to specify the 5-HT(2) subtype selectivity of EGIS-7625 (1-benzyl-4-[(2-nitro-4-methyl-5-amino)-phenyl]-piperazine), a new 5-HT(2B) ligand, in receptor binding studies and characterize its pharmacology at 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors in in vivo experiments and in isolated organs, in vitro. EGIS-7625 had high affinity for recombinant human 5-HT(2B) receptors (pK(i) = 9.0) but much weaker affinity for 5-HT(2A) and 5-HT(2C) receptors (pK(i) = 6.2 and 7.7, respectively). In the classic 5-HT(2B) test, EGIS-7625 produced a concentration-related parallel rightward shift in the concentration-response relationship for the 5-HT-induced smooth muscle constriction in rat stomach fundus strips with a pA(2) of 9.4. On the other hand, EGIS-7625 was a weak competitive antagonist at 5-HT(2A) receptors as it shifted 5-HT-induced concentration-response curves to the right at high concentrations (pA(2) = 6.7) in rabbit pulmonary artery strips. The m-chlorophenylpiperazine-induced hypomotility and hypophagia was only partially attenuated by EGIS-7625 even at a dose of 30 mg/kg i.p. while mianserin, a non-selective 5-HT antagonist was almost fully effective in these tests at 3 mg/kg i.p., suggesting weak antagonistic effect of EGIS-7625 at neuronal 5-HT(2C) receptors, in vivo. In conclusion, EGIS-7625 is a potent, selective and competitive 5-HT(2B) antagonist that seems to be a good research tool for the separation of the functional roles of vascular 5-HT(2A) and 5-HT(2B) receptors.