Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed

Route knowledge and configural knowledge in typical and atypical development: a comparison of sparse and rich environments

Background: Individuals with Down syndrome (DS) and individuals with Williams syndrome (WS) have poor navigation skills, which impact their potential to become independent. Two aspects of navigation were investigated in these groups, using virtual environments (VE): route knowledge (the ability to learn the way from A to B by following a fixed sequence of turns) and configural knowledge (knowledge of the spatial relationships between places within an environment). Methods: Typically developing (TD) children aged 5 to 11 years (N = 93), individuals with DS (N = 29) and individuals with WS (N = 20) were presented with a sparse and a rich VE grid maze. Within each maze, participants were asked to learn a route from A to B and a route from A to C before being asked to find a novel shortcut from B to C. Results: Performance was broadly similar across sparse and rich mazes. The majority of participants were able to learn novel routes, with poorest performance in the DS group, but the ability to find a shortcut, our measure of configural knowledge, was limited for all three groups. That is, 59 % TD participants successfully found a shortcut, compared to 10 % participants with DS and 35 % participants with WS. Differences in the underlying mechanisms associated with route knowledge and configural knowledge and in the developmental trajectories of performance across groups were observed. Only the TD participants walked a shorter distance in the last shortcut trial compared to the first, indicative of increased configural knowledge across trials. The DS group often used an alternative strategy to get from B to C, summing the two taught routes together. Conclusions: Our findings demonstrate impaired configural knowledge in DS and in WS, with the strongest deficit in DS. This suggests that these groups rely on a rigid route knowledge based method for navigating and as a result are likely to get lost easily. Route knowledge was also impaired in both DS and WS groups and was related to different underlying processes across all three groups. These are discussed with reference to limitations in attention and/or visuo-spatial processing in the atypical groups

Palaeoceanographic implications of current-controlled sedimentation in the Alboran Sea after the opening of the Strait of Gibraltar

This study focuses on the Alboran Sea area (Westernmost Mediterranean), where a seismic analysis of the Pliocene and Quaternary stratigraphy was conducted in the Alboran Sea (Westernmost Mediterranean) using ~2000 profiles consisting of single and multi-channel seismic records. The seismic facies and architectural analysis of the deposits evidence the presence of bottom-current deposits (plastered, sheeted, elongated-separated and confined monticular drifts) and associated erosive features (terraces, scarps, moats and channels). Many of these deposits were previously considered to be open slope turbidite deposits which have now been reinterpreted as contourites.The contourite features have developed under the continuous influence of Mediterranean water masses, after the opening of the Strait of Gibraltar (roughly divided into light and dense Mediterranean waters), with plastered drifts dominating on the Spanish and Moroccan continental slopes, and sheeted drifts infilling the subbasins. The location and growth of contourite features have been mainly controlled by two main factors: i) tectonics, which has governed the relocation of the main pathways of the water masses; and ii) climate, which has influenced both water mass conditions and the depth of interfaces, as well as hinterland sediment sources, conditioning the morphoseismic characteristics of the drifts (facies and geometry) and terrace formation (dimensions). The mapping of the contourite facies through time has allowed defining three main scenarios for deep water circulation since the opening of the Strait of Gibraltar, which are: i) Atlantic Zanclean flooding; ii) the Pliocene sea, with two different stages caused by the progressive relocation of flow pathways; and iii) the Quaternary sea, with well defined characteristics and mostly stable flow pathways for the AW, and light and dense Mediterranean waters.This work lead us to consider the geologic framework characterizing the Alboran Sea may have played an important role in the interaction of the Mediterranean Waters before entering the Strait of Gibraltar, and thus in forming the MOW. Additionally, the results of this work may help in understanding the sedimentation in other Mediterranean margins affected by the same water masses and other partly land-locked basins with exchanges of waters over a confining sill

Water mass footprints in uneven turbidite system development in the Alboran Sea

Multidisciplinary work between oceanography, geomorphology and sedimentology has uncovered evidence explaining the uneven development of the turbidite systems (TSs) in the Alboran Sea. Nine TSs have been mapped in the Spanish margin, ranging from sandy to mixed sand-mud fans, and which become sandier towards the Strait of Gibraltar; in contrast TSs do not develop in the Moroccan margin, where three canyons incise the continental slope but there is no TS formation. We interpret that the uneven development of TSs in the two margins and their variable architectures are conditioned by the interaction of alongslope with downslope processes. Two different interaction scenarios with varying intensities are proposed.Versión del edito

(Paleo)circulation models in the Alboran seas during the Pliocene and Quaternary

A multiple Contourite Depositional System has been defined in the Plio-Quaternary sedimentary register in the Alboran Sea. This multiple system formed by the Atlantic and the low density and high density Mediterranean Waters, which shaped the margins and basins since the opening of the Gibraltar Strait. Three different (paleo)circulation scenarios are proposed since then: the Atlantic water Flooding;the Pliocene circulation, characterized by immature low and high density Mediterranean waters and a strong countercurrent in the Western Basin; and the Quaternary circulation, characterized by tabular Mediterranean water masses with multiple current dynamics,an increasing influence of density contrasts, and climate shifts causing major vertical and horizontal displacements of their interfaces.Versión del edito

Mitochondrial variant enrichment from high-throughput single-cell RNA-seq resolves clonal populations

Reconstructing lineage relationships in complex tissues can reveal mechanisms underlying development and disease. Recent methods combine single-cell transcriptomics with mitochondrial DNA variant detection to establish lineage relationships in primary human cells, but are not scalable to interrogate complex tissues. To overcome this limitation, here we develop a technology for high-confidence detection of mitochondrial mutations from high-throughput single-cell RNA-sequencing. We use the new method to identify skewed immune cell expansions in primary human clonal hematopoiesis

Electrophysiological study of local/global processing in Williams syndrome

Persons with Williams syndrome (WS) demonstrate pronounced deficits in visuo-spatial processing. The purpose of the current study was to examine the preferred level of perceptual analysis in young adults with WS (n = 21) and the role of attention in the processing of hierarchical stimuli. Navon-like letter stimuli were presented to adults with WS and age-matched typical controls in an oddball paradigm where local and global targets could appear with equal probability. Participants received no explicit instruction to direct their attention toward a particular stimulus level. Behavioral and event-related potential (ERP) data were recorded. Behavioral data indicated presence of a global precedence effect in persons with WS. However, their ERP responses revealed atypical brain mechanisms underlying attention to local information. During the early perceptual analysis, global targets resulted in reduced P1 and enhanced N150 responses in both participant groups. However, only the typical comparison group demonstrated a larger N150 to local targets. At the more advanced stages of cognitive processing, a larger P3b response to global and local targets was observed in the typical group but not in persons with WS, who instead demonstrated an enhanced P3a to global targets only. The results indicate that in a perceptual task, adults with WS may experience greater than typical global-to-local interference and not allocate sufficient attentional resources to local information

Corrigendum to: Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from EUROAPS registry

Rheumatology 2020;59:1306–1314. doi:https://doi.org/10.1093/rheumatology/kez419 In the original article, the affiliation of co-author Cecilia Beatrice Chighizola should have read: “Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano, IRCCS, Cusano Milanino, Milan, Italy”. These details have been corrected only in this corrigendum to preserve the published version of record

Uncommon genetic syndromes and narrative production - Case Studies with Williams, Smith-Magenis and Prader- Willi Syndromes

This study compares narrative production among three syndromes with genetic microdeletions: Williams syndrome (WS), Smith-Magenis syndrome (SMS), and Prader-Willi syndrome (PWS), characterized by intellectual disabilities and relatively spared language abilities. Our objective is to study the quality of narrative production in the context of a common intellectual disability. To elicit a narrative production, the task Frog! Where Are You was used. Then, structure, process, and content of the narrative process were analysed in the three genetic disorders:WS (n52), SMS (n52), and PWS (n52). Data show evidence of an overall low narrative quality in these syndromes, despite a high variability within different measures of narrative production. Results support the hypothesis that narrative is a highly complex cognitive process and that, in a context of intellectual disability, there is no evidence of particular ‘hypernarrativity’ in these syndromes.This research was supported by the grants FEDER –