De novo missense variants in PPP1CB are associated with intellectual disability and congenital heart disease.

Intellectual disabilities are genetically heterogeneous and can be associated with congenital anomalies. Using whole-exome sequencing (WES), we identified five different de novo missense variants in the protein phosphatase-1 catalytic subunit beta (PPP1CB) gene in eight unrelated individuals who share an overlapping phenotype of dysmorphic features, macrocephaly, developmental delay or intellectual disability (ID), congenital heart disease, short stature, and skeletal and connective tissue abnormalities. Protein phosphatase-1 (PP1) is a serine/threonine-specific protein phosphatase involved in the dephosphorylation of a variety of proteins. The PPP1CB gene encodes a PP1 subunit that regulates the level of protein phosphorylation. All five altered amino acids we observed are highly conserved among the PP1 subunit family, and all are predicted to disrupt PP1 subunit binding and impair dephosphorylation. Our data suggest that our heterozygous de novo PPP1CB pathogenic variants are associated with syndromic intellectual disability.

Discourse on medicine: meditative and calculative approaches to ethics from an international perspective.

Heidegger's two modes of thinking, calculative and meditative, were used as the thematic basis for this qualitative study of physicians from seven countries (Canada, China, India, Ireland, Japan, Korea, & Thailand). Focus groups were conducted in each country with 69 physicians who cared for the elderly. Results suggest that physicians perceived ethical issues primarily through the lens of calculative thinking (76%) with emphasis on economic concerns. Meditative responses represented 24% of the statements and were mostly generated by Canadian physicians whose patients typically were not faced with economic barriers to treatment due to Canada's universal health care system.