LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma

The latent TGFβ-binding proteins (LTBPs) and fibrillins are a superfamily of large, multidomain proteins with structural and TGFβ-signalling roles in the extracellular matrix. Their importance is underscored by fibrillin-1 mutations responsible for Marfan syndrome, but their respective roles are still incompletely understood. We report here on two families where children from healthy, consanguineous parents, presented with megalocornea and impaired vision associated with small, round, dislocated lenses (microspherophakia and ectopia lentis) and myopia, as well as a high-arched palate, and, in older children, tall stature with an abnormally large arm span over body height ratio, that is, associated features of Marfan syndrome. Glaucoma was not present at birth, but was diagnosed in older children. Whole genome homozygosity mapping followed by candidate gene analysis identified homozygous truncating mutations of LTBP2 gene in patients from both families. Fibroblast mRNA analysis was consistent with nonsense-mediated mRNA decay, with no evidence of mutated exon skipping. We conclude that biallelic null LTBP2 mutations cause the ocular phenotype in both families and could lead to Marfan-like features in older children. We suggest that intraocular pressures should be followed-up in young children with an ocular phenotype consisting of megalocornea, spherophakia and/or lens dislocation, and recommend LTBP2 gene analysis in these patients

Rotifers in the Schelde estuary (Belgium): a test of taxonomic relevance

To investigate the reaction of the zooplankton community to improving water quality in the Schelde estuary, we studied the relationship between rotifer species distribution and environmental factors, and the feasibility of using a coarser level of taxonomic resolution. Fifty-two taxa, belonging to 26 genera, were identified, including 22 taxa new for the Schelde. Brachionus calyciflorus, Keratella cochlearis and B. angularis were the most abundant species. The highest diversity and abundances were observed in the freshwater reach. Redundancy analyses (RDA) showed that the main environmental factors explaining rotifer distribution were chlorinity and seasonal factors (discharge levels, cyclopoid abundance). Analysis carried out with data at the species and the genus level gave similar ordination plots, but the positioning of a genus relative to environmental factors did not always adequately represent the associations between the various species within the genus and environmental factors. Similar patterns in space and time were observed using taxonomic richness and diversity indices for analyses at species or genus level. Thus, in the context of the restoration of the Schelde estuary, the identification of rotifer species is very informative, but not essential for detecting important ecological associations

Tidal wetland restoration at Ketenisse polder (Schelde Estuary, Belgium): developments in the first year

Ketenisse polder is a former intertidal brackish marsh (30ha) situated in the mesohaline part of the Schelde Estuary. In the 19th century its central part was embanked as a polder. In the mid 1980’s the area was raised above intertidal level when it was used as a dumping site for the excavated soil from the Liefkenshoek tunnel. In 2002 the area was restored, it was levelled with a weak slope below mean high water level, creating the optimal starting conditions for the development of intertidal mudflats and marshes. Geomorphological changes, sediment characteristics and colonisation by phytobenthos, vegetation, zoobenthos, water birds and breeding birds at the restored site are monitored. The monitoring results of the first year after tidal restoration are presented. Sedimentation as well as erosion between 0 and 30cm was observed in the first year. Local changes in stream current patterns caused erosion on parts of the former mudflats; sheltered depressions filled up relatively fast. Median grain size showed large variation. Organic carbon content of the sediment varied between 0.5 and 15% and was closely related to sediment medium grain size. Chlorophyll a concentrations were negatively correlated with median grain size and tended to increase from the low water line to the shore. They were comparable to nearby intertidal areas and displayed similar seasonal variability with a maximum in spring. The large surface covered wtithVaucheria was indicator of initiated succession towards tidal marsh. Scirpus maritimus and transitional vegetations to Chenopodiaceae-vegetations established with increasing altitude. The Chenopodiaceae-vegetations were relicts of earlier vegetations before the tidal restoration, and will probably disappear. The macrobenthos community was dominated by Oligochaetes, which were present in 73% of all samples and attained an average density of about 40*103 ind. m-2. Other macrobenthos species found were nematods, copepods and Corophium. On the sheltered sampling stations macrobenthic densities were high compared to those on nearby intertidal areas. In the first season, 15 breeding bird species were recorded, the most common species being the Pied Avocet (Recurvirostra avosetta). The most common waterbirds were Common Shelduck (Tadorna tadorna), Greylag Goose (Anser anser), Pied Avocet (Recurvirostra avoset) and Lapwing (Vanellus vanellus), typical species for the mesohaline part of the estuary. The first year’s results suggest that Ketenisse polder has the potential to develop towards a varied and normal functional intertidal area

Isolated and Syndromic Retinal Dystrophy Caused by Biallelic Mutations in RCBTB1, a Gene Implicated in Ubiquitination.

Inherited retinal dystrophies (iRDs) are a group of genetically and clinically heterogeneous conditions resulting from mutations in over 250 genes. Here, homozygosity mapping and whole-exome sequencing (WES) in a consanguineous family revealed a homozygous missense mutation, c.973C>T (p.His325Tyr), in RCBTB1. In affected individuals, it was found to segregate with retinitis pigmentosa (RP), goiter, primary ovarian insufficiency, and mild intellectual disability. Subsequent analysis of WES data in different cohorts uncovered four additional homozygous missense mutations in five unrelated families in whom iRD segregates with or without syndromic features. Ocular phenotypes ranged from typical RP starting in the second decade to chorioretinal dystrophy with a later age of onset. The five missense mutations affect highly conserved residues either in the sixth repeat of the RCC1 domain or in the BTB1 domain. A founder haplotype was identified for mutation c.919G>A (p.Val307Met), occurring in two families of Mediterranean origin. We showed ubiquitous mRNA expression of RCBTB1 and demonstrated predominant RCBTB1 localization in human inner retina. RCBTB1 was very recently shown to be involved in ubiquitination, more specifically as a CUL3 substrate adaptor. Therefore, the effect on different components of the CUL3 and NFE2L2 (NRF2) pathway was assessed in affected individuals' lymphocytes, revealing decreased mRNA expression of NFE2L2 and several NFE2L2 target genes. In conclusion, our study puts forward mutations in RCBTB1 as a cause of autosomal-recessive non-syndromic and syndromic iRD. Finally, our data support a role for impaired ubiquitination in the pathogenetic mechanism of RCBTB1 mutations

High export of dissolved silica from the Greenland Ice Sheet

Silica is an essential element for marine life and plays a key role in the biogeochemistry of the ocean. Glacial activity stimulates rock weathering, generating dissolved silica that is exported to coastal areas along with meltwater. The magnitude of the dissolved silica export from large glacial areas such as the Greenland Ice Sheet is presently poorly quantified and not accounted for in global budgets. Here we present data from two fjord systems adjacent to the Greenland Ice Sheet which reveal a large export of dissolved silica by glacial meltwater relative to other macronutrients. Upscaled to the entire Greenland Ice Sheet, the export of dissolved silica equals 22 ± 10 Gmol Si yr−1. When the silicate-rich meltwater mixes with upwelled deep water, either inside or outside Greenland's fjords, primary production takes place at increased silicate to nitrate ratios. This likely stimulates the growth of diatoms relative to other phytoplankton groups