Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice

BACKGROUND: Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. METHODS: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. RESULTS: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as "potentially pathogenic". Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. CONCLUSIONS: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered "new syndromes" were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype-phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.

Nicht kriegführend, aber doch Teil eines globalen Krieges: Perspektiven auf transnationale Verflechtungen der Schweiz im Ersten Weltkrieg

For a long time national narratives have dominated the histories of the First World War. This was also true in the case of Switzerland, although more recent research has tried to change this. The transnational entanglements of the country during the First World War have, however, not really been focused upon so far. This contribution tries to change this to a certain extent by presenting, on an exemplary basis, some aspects of such entanglements be they economic, humanitarian or politico-diplomatic. Taking into account that global history deals with macro-history as well as micro-history the focus will be on Switzerland’s role in the economic war, on Switzerland and the Hague Conventions at the beginning of the war, on the ICRC and the Agence Internationale des Prisonniers de Guerre, on some humanitarian actors such as Catharina Sturzenegger or Archibald-Rodolphe Reiss, on the extension of state power and the changes of constitutional relations as well as on the exemplary fate of three Swiss living in belligerent countries during the war.

The Swiss Public Initiative against Mass Immigration (‘Masseneinwanderungsinitiative’): Caught between Constitutional Sovereignty and Pacta Sunt Servanda

This article seeks to bring some clarity to the publicly held debate on the Swiss federal popular initiative to limit immigration as it was adopted on 9 February 2014 by the Swiss people. It considers the crux of the matter, which is the implementation of the new Swiss constitutional article in the context of public international law. The initiative is stuck in between Swiss constitutional sovereignty and Swiss treaty obligations flowing from the agreement on free movement of persons between the European Union and the Swiss Confederation. Specific attention is paid to the democratic element anchored in the Swiss Constitution which, in contrast to other systems where the judicial element prevails, is of high importance for whole the process of a bilateral contractual relationship between the European Union and the Swiss Confederation.