DNA methylation epi-signature is associated with two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid syndrome is characterized by a range of neurodevelopmental phenotypes with incomplete penetrance and variable expressivity. It is caused by a variable size and breakpoint microdeletions in the distal long arm of chromosome 22, referred to as 22q13.3 deletion syndrome, including the SHANK3 gene. Genetic defects in a growing number of neurodevelopmental genes have been shown to cause genome-wide disruptions in epigenomic profiles referred to as epi-signatures in affected individuals. RESULTS: In this study we assessed genome-wide DNA methylation profiles in a cohort of 22 individuals with Phelan-McDermid syndrome, including 11 individuals with large (2 to 5.8 Mb) 22q13.3 deletions, 10 with small deletions (< 1 Mb) or intragenic variants in SHANK3 and one mosaic case. We describe a novel genome-wide DNA methylation epi-signature in a subset of individuals with Phelan-McDermid syndrome. CONCLUSION: We identified the critical region including the BRD1 gene as responsible for the Phelan-McDermid syndrome epi-signature. Metabolomic profiles of individuals with the DNA methylation epi-signature showed significantly different metabolomic profiles indicating evidence of two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.

A case of unprovoked, precarious, patent foramen ovale protuberance.

This is a case of a precarious thrombotic mass straddling a patent foramen ovale which had already embolised to the pulmonary circulation. The diagnosis was initially deceptive and management challenging. LEARNING POINTS: Echocardiography is mandated and can change management in haemodynamically unstable patients with pulmonary emboli.Pulmonary embolism can be life-threatening.The authors propose that urgent cardiac surgery is the safest treatment in the setting of highly mobile, large volume, intra-cardiac thrombus.

A survey of Core Medical Trainees' opinions on the ePortfolio record of educational activities: beneficial and cost-effective?

OBJECTIVES: To evaluate Core Medical Trainees' (CMTs) opinions on the role of the ePortfolio in postgraduate education. DESIGN AND SETTING: Cross-sectional survey of 91 CMTs in five NHS trusts within the South Thames Deanery. PARTICIPANTS: Completed surveys were received from 80 Core Medical Trainees. RESULTS: A total of 84% agreed that an ongoing record of progress is necessary, only 5% felt the ePortfolio represents value for money; 78% of respondents were unclear as to how the Freedom of Information Act (2000) impacts on the ePortfolio, and most were uninformed of the extent to which their entries can be accessed by third parties. CONCLUSIONS: Trainees recognise the importance of recording ongoing progress, but most consider the ePortfolio to be poor value for money. There is uncertainty regarding ownership of information held on ePortfolio, and to what extent it can be accessed. There are inadequate opportunities to discuss concerns. This requires further deliberation and until things are clarified, trainees may not fully engage with the resource.

Anatomical perspectives on adult neural stem cells.

The concept of stem cells within the adult brain is not new. However, only recently have scientific techniques become sufficiently advanced to identify them although this remains problematic and the technology is still developing. Nevertheless, it is now generally recognized that stem cells are restricted to two germinal regions within the intact brain. From here they can migrate to specific destinations where they integrate with existing circuitry. Their identity remains controversial but a growing body of evidence suggests it may have an astrocytic phenotype. Within the germinal regions the stem cells are confined to a niche environment and are capable of responding to environmental signals generated locally in an autocrine or paracrine fashion. The niche environment is also modulated by more generalized systemic and physiological activity. These observations are exciting in their own right and form the basis of this review. They are also beginning to alter how we think about neural injury and disease and to impact on the development of novel therapies.