PurposeCoffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported... Show morePurposeCoffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort.MethodsClinical symptoms for 41 novel and 24 previously published affected individuals were analyzed using the Human Phenotype Ontology. For genotype-phenotype correlations, molecular data were standardized and grouped into non-truncating and likely gene-disrupting (LGD) variants. Missense variant protein expression and BAF-subunit interactions were examined using 3D protein modeling, co-immunoprecipitation, and proximity-ligation assays.ResultsNeurodevelopmental delay with intellectual disability, muscular hypotonia, and behavioral disorders were the major manifestations. Clinical hallmarks of BAFopathies were rare. Clinical presentation differed significantly, with LGD variants being predominantly inherited and associated with mildly reduced or normal cognitive development, whereas non-truncating variants were mostly de novo and presented with severe developmental delay. These distinct manifestations and non-truncating variant clustering in functional domains suggest different pathomechanisms. In vitro testing showed decreased protein expression for N-terminal missense variants similar to LGD.ConclusionThis study improved SMARCC2 variant classification and identified discernible SMARCC2-associated phenotypes for LGD and non-truncating variants, which were distinct from other BAFopathies. The pathomechanism of most non-truncating variants has yet to be investigated. Show less
Existing research on intra-party unity and conflict has mostly focused on (dis)unity within the legislative branch of the party at the national level, while neglecting conflict between the... Show moreExisting research on intra-party unity and conflict has mostly focused on (dis)unity within the legislative branch of the party at the national level, while neglecting conflict between the different faces or at different levels of the party. Intra-party unity and conflict have also been routinely defined and operationalized through ideological homogeneity or distance, although intra-party conflicts are multidimensional and dynamic phenomena. The articles included in this special issue seek to address these shortcomings in the literature. Their contributions are threefold: (1) they theorize intra-party conflict as a dynamic and multifaceted concept; (2) they explore conflicts across and between several party faces, and among different intra-party actors; (3) they investigate the determinants and management of conflict at several party levels. Show less
