SNP array typing provides new insights in chromosomal nondisjunction

Background Maternal uniparental disomy (UPD) of chromosome 7 (upd(7)mat) accounts for approximately 10% of patients with Silver-Russell syndrome (SRS). For upd(7)mat and trisomy 7, a significant number of mechanisms have been proposed to explain the postzygotic formation of these chromosomal compositions, but all have been based on as small number of cases. To obtain the ratio of isodisomy and heterodisomy in UPDs (hUPD, iUPD) and to determine the underlying formation mechanisms, we analysed a large cohort of upd(7)mat patients (n = 73) by SNP array typing. Based on these data, we discuss the UPDs and their underlying trisomy 7 formation mechanisms. Results A whole chromosome 7 maternal iUPD was confirmed in 28.8%, a mixture or complete maternal hUPD in 71.2% of patients. Conclusions We could demonstrate that nondisjunction mechanism affecting chromosome 7 are similar to that of the chromosomes more frequently involved in trisomy (and/or UPD), and that mechanisms other than trisomic rescue have a lower significance than previously suspected. Furthermore, we suggest SNP array typing for future parent- and cell-stage-of origin studies in human aneuploidies as they allow the definite classification of trisomies and UPDs, and provide information on recombinational events and their suggested association with aneuploidy formation

Congenital imprinting disorders: EUCID.net - a network to decipher their aetiology and to improve the diagnostic and clinical care.

Imprinting disorders (IDs) are a group of eight rare but probably underdiagnosed congenital diseases affecting growth, development and metabolism. They are caused by similar molecular changes affecting regulation, dosage or the genomic sequence of imprinted genes. Each ID is characterised by specific clinical features, and, as each appeared to be associated with specific imprinting defects, they have been widely regarded as separate entities. However, they share clinical characteristics and can show overlapping molecular alterations. Nevertheless, IDs are usually studied separately despite their common underlying (epi)genetic aetiologies, and their basic pathogenesis and long-term clinical consequences remain largely unknown. Efforts to elucidate the aetiology of IDs are currently fragmented across Europe, and standardisation of diagnostic and clinical management is lacking. The new consortium EUCID.net (European network of congenital imprinting disorders) now aims to promote better clinical care and scientific investigation of imprinting disorders by establishing a concerted multidisciplinary alliance of clinicians, researchers, patients and families. By encompassing all IDs and establishing a wide ranging and collaborative network, EUCID.net brings together a wide variety of expertise and interests to engender new collaborations and initiatives

Recent Advances in Imprinting Disorders.

Imprinting disorders (ImpDis) are a group of currently 12 congenital diseases with common underlying (epi)genetic etiologies and overlapping clinical features affecting growth, development and metabolism. In the last years it has emerged that ImpDis are characterized by the same types of mutations and epimutations, i.e. uniparental disomies, copy number variations, epimutations, and point mutations. Each ImpDis is associated with a specific imprinted locus, but the same imprinted region can be involved in different ImpDis. Additionally, even the same aberrant methylation patterns are observed in different phenotypes. As some ImpDis share clinical features, clinical diagnosis is difficult in some cases. The advances in molecular and clinical diagnosis of ImpDis help to circumvent these issues, and they are accompanied by an increasing understanding of the pathomechanism behind them. As these mechanisms have important roles for the etiology of other common conditions, the results in ImpDis research have a wider effect beyond the borders of ImpDis. For patients and their families, the growing knowledge contributes to a more directed genetic counseling of the families and personalized therapeutic approaches.COST (BM1208), Bundesministerium für Bildung und Forschung (Network ‘Imprinting Diseases’, 01GM1513B), German Ministry of research and education (01GM1513B)This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/cge.1282

Genetic regulation of pituitary gland development in human and mouse

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans

Octobre 42 à la Bibliothèque nationale : Des faits de collaboration par les livres

Ce colloque s’est tenu les jeudi et vendredi 23 et 24 mars 2017, à la Bibliothèque universitaire des langues et civilisations et à la Bibliothèque nationale de France, Il a été organisé par le Centre Gabriel Naudé de l\u27Ecole nationale supérieure des sciences de l\u27information et des bibliothèques (ENSSIB), l\u27Institut d\u27histoire du temps présent (IHTP, UMR CNRS Paris 8) et l\u27Université Paris Diderot (EA Identités, cultures, territoires), avec le soutien de la Bibliothèque nationale de France, de la Bibliothèque universitaire des langues et civilisations (BULAC), de la Fondation pour la Mémoire de la Shoah, de la Claims Foundation, de la Fondation Maison des Sciences de l\u27Homme et du Deutscher Akademischer Austauschdienst. Au cours de ce colloque, une douzaine de livres, datant du XVIIe siècle et retrouvés dans ses collections par la Bibliothèque centrale et régionale de Berlin (Zentral -und Landesbibliothek) ont été restitués à trois ministères français (ministère des Affaires étrangères, ministère de l\u27Intérieur, ministère de la Justice) auxquels ils avaient été spoliées en juin 1940. Un registre manuscrit d\u27état civil des années 1751-1771, spolié à la commune de Verpel (Ardennes) lui sera également restitué. Associé à ce colloque en ligne, les Presses de l’Enssib proposent Où sont les bibliothèques françaises spoliées par les nazis ? ouvrage coordonné par Martine Poulain qui a rassemblé les contributions, enrichies, concernant particulièrement l’histoire d’environ 14 000 livres spoliés et déposés dans une quarantaine de bibliothèques françaises entre 1950 et 1953, et leurs caractéristiques. https://presses.enssib.fr/catalogue/ou-sont-les-bibliotheques-francaises-spoliees-par-les-nazi

EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders: Silver–Russell and Beckwith–Wiedemann syndrome

Molecular genetic testing for the 11p15-associated imprinting disorders Silver–Russell and Beckwith–Wiedemann syndrome (SRS, BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. With the growing knowledge on the molecular basis of these disorders and the demand for molecular testing, it turned out that there is an urgent need for a standardized molecular diagnostic testing and reporting strategy. Based on the results from the first external pilot quality assessment schemes organized by the European Molecular Quality Network (EMQN) in 2014 and in context with activities of the European Network of Imprinting Disorders (EUCID.net) towards a consensus in diagnostics and management of SRS and BWS, best practice guidelines have now been developed. Members of institutions working in the field of SRS and BWS diagnostics were invited to comment, and in the light of their feedback amendments were made. The final document was ratified in the course of an EMQN best practice guideline meeting and is in accordance with the general SRS and BWS consensus guidelines, which are in preparation. These guidelines are based on the knowledge acquired from peer-reviewed and published data, as well as observations of the authors in their practice. However, these guidelines can only provide a snapshot of current knowledge at the time of manuscript submission and readers are advised to keep up with the literature

Not Fit for Hire: The United States and France on Weight Discrimination in Employment

Part I will examine past and present attitudes regarding obesity in US society and will discuss the employment challenges obese individuals face because of weight discrimination. Further, Part I will survey US statutory laws at the federal, state, and local levels that currently protect against particular instances of weight discrimination. In sum, this Part aims to provide the current legal and social landscape in the United States for protecting individuals against employment discrimination based on their weight. Part II will look at France’s cultural bias against obesity and its laws against physical appearance discrimination. Part II then will analyze French statutory law and legislative history. This Part will ground the discussion in cases that have arisen in French media involving physical appearance discrimination based on weight, including an investigation by France’s human rights watch institution, Le Défenseur des droits. Overall, this perspective on French law will form the foundation for analyzing the extent of protection that the United States may feasibly adopt to protect individuals against weight discrimination. Part III juxtaposes France’s laws prohibiting physical appearance discrimination with current US federal law to highlight the ways in which the United States falls short of its promise of equal protection for all by permitting employment discrimination based on an individual’s weight. This Part posits that US law may serve as a tool to catalyze important social change in the public’s perception of obesity, based on a similar shift in public perception that occurred in France following the adoption of its laws prohibiting physical appearance discrimination. Ultimately, this Note argues that the United States must act to eliminate the pervasive discrimination against obese individuals by passing national legislation making employment decisions based on weight unlawful

Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci.

Congenital imprinting disorders (IDs) are characterised by molecular changes affecting imprinted chromosomal regions and genes, i.e. genes that are expressed in a parent-of-origin specific manner. Recent years have seen a great expansion in the range of alterations in regulation, dosage or DNA sequence shown to disturb imprinted gene expression, and the correspondingly broad range of resultant clinical syndromes. At the same time, however, it has become clear that this diversity of IDs has common underlying principles, not only in shared molecular mechanisms, but also in interrelated clinical impacts upon growth, development and metabolism. Thus, detailed and systematic analysis of IDs can not only identify unifying principles of molecular epigenetics in health and disease, but also support personalisation of diagnosis and management for individual patients and families.All authors are members of the EUCID.net network, funded by COST (BM1208). TE is funded by the German Ministry of research and education (01GM1513B). GPdN is funded by I3SNS Program of the Spanish Ministry of Health (CP03/0064; SIVI 1395/09), Instituto de Salud Carlos III (PI13/00467) and Basque Department of Health (GV2014/111017).This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13148-015-0143-