Biallelic variants in ADAMTS15 cause a novel form of distal arthrogryposis

Purpose We aimed to identify the underlying genetic cause for a novel form of distal arthrogryposis. Methods Rare variant family-based genomics, exome sequencing, and disease-specific panel sequencing were used to detect ADAMTS15 variants in affected individuals. Adamts15 expression was analyzed at the single-cell level during murine embryogenesis. Expression patterns were characterized using in situ hybridization and RNAscope. Results We identified homozygous rare variant alleles of ADAMTS15 in 5 affected individuals from 4 unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. Radiographic investigations showed physiological interphalangeal joint morphology. Additional features included knee, Achilles tendon, and toe contractures, spinal stiffness, scoliosis, and orthodontic abnormalities. Analysis of mouse whole-embryo single-cell sequencing data revealed a tightly regulated Adamts15 expression in the limb mesenchyme between embryonic stages E11.5 and E15.0. A perimuscular and peritendinous expression was evident in in situ hybridization in the developing mouse limb. In accordance, RNAscope analysis detected a significant coexpression with Osr1, but not with markers for skeletal muscle or joint formation. Conclusion In aggregate, our findings provide evidence that rare biallelic recessive trait variants in ADAMTS15 cause a novel autosomal recessive connective tissue disorder, resulting in a distal arthrogryposis syndrome

EU-wide methodology to map and assess ecosystem condition

The EU Biodiversity Strategy for 2030 calls for developing an EU-wide methodology to map, assess and achieve good condition of ecosystems, so they can deliver benefits to society through the provision of ecosystem services. The EU-wide methodology presented in this report addresses this methodological gap. The EU-wide methodology has adopted the System of Environmental Economic Accounting - Ecosystem Accounting (SEEA EA) as reference framework. The SEEA EA is an integrated framework for organizing biophysical information about ecosystems, adopted as a global statistical standard by the United Nations. The SEEA EA is also the reference framework under the proposal for the amendment of Regulation (EU) No 691/2011 on European environmental economic accounts. Building on previous work done within the MAES initiative, the EU-wide methodology presents useful insights to operationalise the SEEA EA at EU level by integrating different EU data streams in a consistent way with this global statistical standard to consistently map and assess ecosystem condition in the EU across all ecosystem types. The adoption of the SEEA EA framework offers the flexibility to integrate different data flows, leveraging the use of available EU data, such as data reported by MS under EU legislation and EU geospatial data. The EU-wide methodology. The implementation of the EU-wide methodology, making use of available data, will provide the scientific knowledge base to support a range of policies and legal instruments