Rare Deletions at 16p13.11 Predispose to a Diverse Spectrum of Sporadic Epilepsy Syndromes

Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls. Large deletions (> 100 kb) at 16p13.11 were observed in 23 patients, whereas no control had a deletion greater than 16 kb. Patients, even those with identically sized 16p13.11 deletions, presented with highly variable epilepsy phenotypes. For a subset of patients with a 16p13.11 deletion, we show a consistent reduction of expression for included genes, suggesting that haploinsufficiency might contribute to pathogenicity. We also investigated another possible mechanism of pathogenicity by using hybridization-based capture and next-generation sequencing of the homologous chromosome for ten 16p13.11-deletion patients to look for unmasked recessive mutations. Follow-up genotyping of suggestive polymorphisms failed to identify any convincing recessive-acting mutations in the homologous interval corresponding to the deletion. The observation that two of the 16p13.11 deletions were larger than 2 Mb in size led us to screen for other large deletions. We found 12 additional genomic regions harboring deletions > 2 Mb in epilepsy patients, and none in controls. Additional evaluation is needed to characterize the role of these exceedingly large, non-locus-specific deletions in epilepsy. Collectively, these data implicate 16p13.11 and possibly other large deletions as risk factors for a wide range of epilepsy disorders, and they appear to point toward haploinsufficiency as a contributor to the pathogenicity of deletions

The PLATO Mission

International audiencePLATO (PLAnetary Transits and Oscillations of stars) is ESA's M3 mission designed to detect and characterise extrasolar planets and perform asteroseismic monitoring of a large number of stars. PLATO will detect small planets (down to <2 R_(Earth)) around bright stars (<11 mag), including terrestrial planets in the habitable zone of solar-like stars. With the complement of radial velocity observations from the ground, planets will be characterised for their radius, mass, and age with high accuracy (5 %, 10 %, 10 % for an Earth-Sun combination respectively). PLATO will provide us with a large-scale catalogue of well-characterised small planets up to intermediate orbital periods, relevant for a meaningful comparison to planet formation theories and to better understand planet evolution. It will make possible comparative exoplanetology to place our Solar System planets in a broader context. In parallel, PLATO will study (host) stars using asteroseismology, allowing us to determine the stellar properties with high accuracy, substantially enhancing our knowledge of stellar structure and evolution. The payload instrument consists of 26 cameras with 12cm aperture each. For at least four years, the mission will perform high-precision photometric measurements. Here we review the science objectives, present PLATO's target samples and fields, provide an overview of expected core science performance as well as a description of the instrument and the mission profile at the beginning of the serial production of the flight cameras. PLATO is scheduled for a launch date end 2026. This overview therefore provides a summary of the mission to the community in preparation of the upcoming operational phases

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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