The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction

Purpose: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. Methods: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. Results: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55α subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55α but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. Conclusion: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported

Ecological-economic analysis of wetlands; scientific integration for management and policy

Wetlands all over the world have been lost or are threatened in spite of various international agreements and national policies. This is caused by: (1) the public nature of many wetlands products and services; (2) user externalities imposed on other stakeholders; and (3) policy intervention failures that are due to a lack of consistency among government policies in different areas (economics, environment, nature protection, physical planning, etc.). All three causes are related to information failures which in turn can be linked to the complexity and 'invisibility' of spatial relationships among groundwater, surface water and wetland vegetation. Integrated wetland research combining social and natural sciences can help in part to solve the information failure to achieve the required consistency across various government policies. An integrated wetland research framework suggests that a combination of economic valuation, integrated modelling, stakeholder analysis, and multi-criteria evaluation can provide complementary insights into sustainable and welfare-optimising wetland management and policy. Subsequently, each of the various components of such integrated wetland research is reviewed and related to wetland management policy