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.

The Benefits of Multilingualism for Statutory and Constitutional Interpretation in South Africa

Taking the South African experience as an example, this article considers the interpretive benefits to be reaped from having access to bi- and multilingual versions of a statutory text. The discussion takes place against the backdrop of a history of statutory bi- and multilingualism in the said jurisdiction as well as, at present, constitutional guarantees of language rights and the “parity of esteem” of eleven official languages. It is argued that, if invoked with due discretion and in a non-rigid way, statutory multilingualism can be a boon to statutory and constitutional interpretation. The South African courts – whose traditional approach to statutory inter-pretation has tended to be literalist, formalistic and formulaic – are, generally speaking, to be commended for their supple use of bilingualism as an aid to interpretation over the years. The advent of constitutional multilingualism and the (potential) availability of statutory texts (and the Constitution) in more than two languages, have moreover created conditions conducive to the further development and refinement of reliance on multilingualism in statutory and constitutional interpretation – certain challenges notwithstanding.

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.

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 999 - Reaktion auf die Rede Gwinners bei den Feierlichkeiten zum 100. Geburtstag Schopenhauers

u.a. Niederschlag der Feier in Zeitungen;