CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Nannofossils: the smoking gun for the Canarian hotspot

The origin of volcanism in the Canary Islands has been a matter of controversy for several decades. Discussions have hinged on whether the Canaries owe their origin to seafloor fractures associated with the Atlas Mountain range or to an underlying plume or hotspot of superheated mantle material. However, the debate has recently come to a conclusion following the discovery of nannofossils preserved in the products of the 2011–2012 submarine eruption at El Hierro, which tell us about the age and growth history of the western‐most island of the archipelago. Light coloured, pumice‐like ‘floating rocks’ were found on the sea surface during the first days of the eruption and have been shown to contain fragments of pre‐island sedimentary strata. These sedimentary rock fragments were picked up by ascending magma and transported to the surface during the eruption, and remarkably retained specimens of pre‐island Upper Cretaceous to Pliocene calcareous nannofossils (e.g. coccolithophores). These marine microorganisms are well known biostratigraphical markers and now provide crucial evidence that the westernmost and youngest island in the Canaries is underlain by the youngest sediment relative to the other islands in the archipelago. This finding supports an age progression for the onset of volcanism at the individual islands of the archipeligo. Importantly, as fracture‐related volcanism is known to produce non‐systematic age‐distributions within volcanic alignments, the now‐confirmed age progression corroberates to the relative motion of the African plate over an underlying mantle plume or hotspot as the cause for the present‐day Canary volcanism.This work contributes to the efforts of the Centre of Natural Disaster Science (CNDS) at Uppsala University. We are also grateful to the Royal Swedish Academy of Science (KVA), the Swedish Science Foundation (VR), the Canarian Government, and the Spanish CSIC and MINECO for generous financial support.Peer Reviewe

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission. © 2019, The Author(s)