Lehetőségek és veszélyek az offshore-jelenségben = Opportunities and Risks in the Offshore Phenomenon

A tanulmány az offshore-jelenséget vizsgálja átfogóan, az adózási kérdésekkel összefüggésben. Az offshore kifejezés jelentéstartalma sokkal árnyaltabb, mint ahogyan a köztudatban él, a kormányzatok számára újabb gazdaságpolitikai eszközöket jelent. A nemzetközi tőkepiaci tranzakciók esetében az onshore és offshore státusz a tőkepiacokhoz való fokozatos hozzáférés egyes szintjeit különíti el. A szerzők felvetnek néhány, adó- és társasági jogi szempontból is fontos kérdést az offshore-ral kapcsolatban. Foglalkoznak az adóparadicsomok kialakulásának történetével, az adókikerülés és az adóoptimalizáció fogalmának meghatározása körüli nehézségekkel, valamint egy gyakorlati példán keresztül ismertetik, hogy milyen módon lehetséges az offshore cégek segítségével kijátszani a jogszabályokat

Súlyos epilepsziás encephalopathia hátterében azonosított MECP2-gén-mutáció fiúbetegben = MECP2 mutation in a male patient identified in the background of severe epileptic encephalopathy

Absztrakt: A szerzők egy negatív családi anamnézisű, súlyos, neonatalis kezdetű epilepsziás encephalopathiában szenvedő, jelenleg kétéves fiúgyermek esetét mutatják be. A terápiarezisztens epilepszia és az igen súlyos fejlődésbeli elmaradás etiológiáját kiterjedt klinikai vizsgálatokkal sem sikerült tisztázni. Genetikai okot feltételezve, külföldi genetikai laboratóriumban 128 gént tartalmazó újgenerációs szekvenálási (NGS-) panelvizsgálatot indikáltak epilepsziás encephalopathiát okozó betegségek irányában. A vizsgálat egy eddig ismeretlen hemizigóta misszensz mutációt igazolt a MECP2-génben. A szerzők az esetbemutatás kapcsán áttekintik a lányokban klasszikusan Rett-szindrómát okozó, a MECP2-gén mutációi által előidézett idegfejlődési rendellenességek spektrumát fiúkban. Más, X-hez kötött domináns öröklődésű betegségekhez hasonlóan sokáig úgy gondolták, hogy a MECP2-gén-mutációt hordozó fiúmagzatok életképtelenek, napjainkra azonban ez a nézet megváltozott. A szerzők úgy tudják, hogy betegük az első magyar fiúgyermek, akinél a MECP2-gén mutációja igazolódott. Orv Hetil. 2019; 160(51): 2036–2039. | Abstract: Here we report on a severe, neonatal onset epileptic encephalopathy manifested in a currently 2-year-old boy with no family history of neurological disease. Extensive clinical investigations were unable to clarify the etiology of the infant’s condition characterized by drug-resistant seizures and markedly delayed developmental skills. As in this class of disorders a genetic cause might be identified, a next-generation sequencing (NGS) epilepsy panel examination consisting of 128 genes was initiated for a correct diagnosis. The genetic analysis identified a previously undescribed hemizygous missense mutation in the MECP2 gene. Similarly to other, X-linked dominant disorders, Rett syndrome was originally hypothesized to be lethal in males. This theory, however, has been revised. The aim of this report is to review the wide spectrum of neurodevelopmental diseases observed in male patients carrying mutations in the MECP2 gene classically associated with Rett syndrome in girls. To the author’s knowledge, this is the first report in Hungary to document MECP2 mutation of a male patient diagnosed by molecular genetic testing. Orv Hetil. 2019; 160(51): 2036–2039

Novel phenotypic variant in the MYH7 spectrum due to a stop-loss mutation in the C-terminal region: a case report

Abstract Background Defects of the slow myosin heavy chain isoform coding MYH7 gene primarily cause skeletal myopathies including Laing Distal Myopathy, Myosin Storage Myopathy and are also responsible for cardiomyopathies. Scapuloperoneal and limb-girdle muscle weakness, congenital fiber type disproportion, multi-minicore disease were also reported in connection of MYH7. Pathogeneses of the defects in the head and proximal rod region of the protein are well described. However, the C-terminal mutations of the MYH7 gene are less known. Moreover, only two articles describe the phenotypic impact of the elongated mature protein product caused by termination signal loss. Case presentation Here we present a male patient with an unusual phenotypic variant of early-onset and predominant involvement of neck muscles with muscle biopsy indicating myopathy and sarcoplasmic storage material. Cardiomyopathic involvements could not be observed. Sequencing of MYH7 gene revealed a stop-loss mutation on the 3-prime end of the rod region, which causes the elongation of the mature protein. Conclusions The elongated protein likely disrupts the functions of the sarcomere by multiple functional abnormalities. This elongation could also affect the thick filament degradation leading to protein deposition and accumulation in the sarcomere, resulting in the severe myopathy of certain axial muscles. The phenotypic expression of the detected novel MYH7 genotype could strengthen and further expand our knowledge about mutations affecting the structure of MyHCI by termination signal loss in the MYH7 gene

Revealing the impact of the Caucasus region on the genetic legacy of Romani people from genome-wide data.

Romani people are a significant minority in Europe counting about 10 million individuals scattered throughout the continent. They are a migratory group originating from Northwestern India. Their exodus from India occurred approximately 1000-1500 years ago. The migration route of the Romani people was reconstructed with the help of cultural anthropology, linguistics and historical records. Their migration made them through Central Asia, Middle East and the Caucasus region, prior to the arriving into Europe. Yet the significance of these regions, especially of the Caucasus, in Roma ancestry was a rather neglected topic. Contribution of the Caucasus and further affected regions to the ancestry of Roma was investigated based on genome-wide autosomal marker data. 158 European Roma samples and 41 populations from the Caucasus region, from Middle East, Central Asia and from South Asia were considered in our tests. Population structure and ancestry analysis algorithms were applied to investigate the relationship of Roma with these populations. Identical by descent DNA segment analyses and admixture linkage disequilibrium based tests were also applied. Our results suggest that the Caucasus region plays also a significant role in the genetic legacy of Romani people besides the main sources, Europe and South Asia, previously investigated by other population genetic studies. The Middle East and Central Asia seems slightly less important but far from negligible in connection with the sources of Roma ancestry. Our results point out that the Caucasus region and altogether the area of the Caspian and Black Seas had a significant role in the migration of Romani people towards Europe and contributed significantly to the genetic legacy of Roma rival to the European and Indian main sources

Correction to: Novel phenotypic variant in the MYH7 spectrum due to a stop-loss mutation in the C-terminal region: a case report

Abstract Following publication of the original article [1], the authors requested a correction to the details of one of the co-authors

Down-Syndrome-Related Maternal Dysbiosis Might Be Triggered by Certain Classes of Antibiotics: A New Insight into the Possible Pathomechanisms

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

Characterization of Danube Swabian population samples on a high-resolution genome-wide basis

Abstract Background German-derived ethnicities are one of the largest ethnic groups in Hungary, dating back to the formation of the Kingdom of Hungary, which took place at the beginning of the 11th century. Germans arrived in Hungary in many waves. The most significant immigration wave took place following the collapse of the Ottoman Empire in East-Central Europe which closed the 150 year long Ottoman occupation. To date, there are no comprehensive genome-wide studies investigating the genetic makeup of the Danube Swabians. Here we analyzed 47 Danube Swabian samples collected from elderly Swabian individuals living in the Dunaszekcső-Bár area, in Danube side villages of Southwest Hungary. These Swabians, according to self-declaration, did not admix with other ethnic groups for 3–6 succeeding generations. Using Illumina Infinium 720 K Beadchip genotype data, we applied allele frequency-based and haplotype-based genome-wide marker data analyses to investigate the ancestry and genetic composition of the collected Danube Swabian samples. Results Haplotype-based analyses like identity by descent segment analysis show that the investigated Danube Swabians possess significant German and other West European ancestry, but their Hungarian ancestry is also prominent. Our results suggest that their main source of ancestry can be traced back to Western Europe, presumably to the region of Germany. Conclusion This is the first analysis of Danube Swabian population samples based on genome-wide autosomal data. Our results establish the basis for conducting further comprehensive research on Danube Swabians and on other German ethnicities of the Carpathian basin, which can help reconstruct their origin, and identify their major archaic genomic patterns