Mutations in ZMYND10, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms in Humans and Flies, Cause Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger resequencing in PCD-affected families afflicted with combined IDA and ODA defects, we found that 6/38 (16%) carried biallelic mutations in the conserved zinc-finger gene BLU (ZMYND10). ZMYND10 mutations conferred dynein-arm loss seen at the ultrastructural and immunofluorescence level and complete cilia immotility, except in hypomorphic p.Val16Gly (c.47T>G) homozygote individuals, whose cilia retained a stiff and slowed beat. In mice, Zmynd10 mRNA is restricted to regions containing motile cilia. In a Drosophila model of PCD, Zmynd10 is exclusively expressed in cells with motile cilia: chordotonal sensory neurons and sperm. In these cells, P-element-mediated gene silencing caused IDA and ODA defects, proprioception deficits, and sterility due to immotile sperm. Drosophila Zmynd10 with an equivalent c.47T>G (p.Val16Gly) missense change rescued mutant male sterility less than the wild-type did. Tagged Drosophila ZMYND10 is localized primarily to the cytoplasm, and human ZMYND10 interacts with LRRC6, another cytoplasmically localized protein altered in PCD. Using a fly model of PCD, we conclude that ZMYND10 is a cytoplasmic protein required for IDA and ODA assembly and that its variants cause ciliary dysmotility and PCD with laterality defects

European Resuscitation Council Guidelines 2021: Ethics of resuscitation and end of life decisions

These European Resuscitation Council Ethics guidelines provide evidence-based recommendations for the ethical, routine practice of resuscitation and end-of-life care of adults and children. The guideline primarily focus on major ethical practice interventions (i.e. advance directives, advance care planning, and shared decision making), decision making regarding resuscitation, education, and research. These areas are tightly related to the application of the principles of bioethics in the practice of resuscitation and end-of-life care. © 202

Ethics of resuscitation and end of life decisions: European Resuscitation Council Guidelines 2021 [Ethik der Reanimation und Entscheidungen am Lebensende: Leitlinien des European Resuscitation Council 2021]

These European Resuscitation Council Ethics guidelines provide evidence-based recommendations for the ethical, routine practice of resuscitation and end-of-life care of adults and children. The guideline primarily focus on major ethical practice interventions (i.e. advance directives, advance care planning, and shared decision making), decision making regarding resuscitation, education, and research. These areas are tightly related to the application of the principles of bioethics in the practice of resuscitation and end-of-life care. © 2021, European Resuscitation Council (ERC), German Resuscitation Council (GRC), Austrian Resuscitation Council (ARC)