A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus

The expression of imprinted genes is mediated by allele-specific epigenetic modification of genomic DNA and chromatin, including parent of origin-specific DNA methylation. Dysregulation of these genes causes a range of disorders affecting pre- and post-natal growth and neurological function. We investigated a cohort of 12 patients with transient neonatal diabetes whose disease was caused by loss of maternal methylation at the TNDM locus. We found that six of these patients showed a spectrum of methylation loss, mosaic with respect to the extent of the methylation loss, the tissues affected and the genetic loci involved. Five maternally methylated loci were affected, while one maternally methylated and two paternally methylated loci were spared. These patients had higher birth weight and were more phenotypically diverse than other TNDM patients with different aetiologies, presumably reflecting the influence of dysregulation of multiple imprinted genes. We propose the existence of a maternal hypomethylation syndrome, and therefore suggest that any patient with methylation loss at one maternally-methylated locus may also manifest methylation loss at other loci, potentially complicating or even confounding the clinical presentation.<br/

A Modern View on the Red Sea Rift: Tectonics, Volcanism and Salt Blankets

Continental rifting and ocean basin formation can be observed at the present day in the Red Sea, which is used as the modern analogue for the formation of mid-ocean ridges. Competing theories for how spreading begins—either by quasi-instantaneous formation of a whole spreading segment or by initiation of spreading at multiple discrete “nodes” separated by thinned continental lithosphere—have been put forward based, until recently, on the observations that many seafloor features and geophysical anomalies (gravity, magnetics) along the axis of the Red Sea appeared anomalous compared to ancient and modern examples of ocean basins in other parts of the world. The latest research shows, however, that most of the differences between the Red Sea Rift (RSR) and other (ultra)slow-spreading mid-ocean ridges can be related to its relatively young age and the presence and movement of giant submarine salt flows that blanket large portions of the rift valley. In addition, the geophysical data that was previously used to support the presence of continental crust between the axial basins with outcropping oceanic crust (formerly named “spreading nodes”) can be equally well explained by processes related to the sedimentary blanketing and hydrothermal alteration. The observed spreading nodes are not separated from one another by tectonic boundaries but rather represent “windows” onto a continuous spreading axis which is locally inundated and masked by massive slumping of sediments or evaporites from the rift flanks. Volcanic and tectonic morphologies are comparable to those observed along slow and ultra-slow spreading ridges elsewhere and regional systematics of volcanic occurrences are related to variations in volcanic activity and mantle heat flow. Melt-salt interaction due to salt flows, that locally cover the active spreading segments, and the absence of large detachment faults as a result of the nearby Afar plume are unique features of the RSR. The differences and anomalies seen in the Red Sea still may be applicable to all young oceanic rifts, associated with plumes and/or evaporites, which makes the Red Sea a unique but highly relevant type example for the initiation of slow rifting and seafloor spreading and one of the most interesting targets for future ocean research