A Decade of Protecting Progress: Ethics Review.

Ethics Review began a decade ago with a mission to identify ethical concerns that hold back innovation and to promote solutions that would move the field forward. Over this time, blood biomarkers for brain pathology and medications that treat that pathology promise to transform research and care. A central problem is that the evidence needed to guide test interpretation and practice is accumulating and there are unanswered questions. At the same time, people living with and at risk for dementia want access to their test results and involvement in their care. We promote dialog among diverse people across many institutions through collaboration with the Advisory Group on Risk Evidence Education for Dementia (AGREEDementia.org). Over the years Ethics Review continues to publish these dialogs and solutions to overcome the paralysis of indecision and ethical concerns.

Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies.

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.