Journal article

De novo missense variants in RAC3 cause a novel neurodevelopmental syndrome

Gregory Costain, Bert Callewaert, Heinz Gabriel, Tiong Y Tan, Susan Walker, John Christodoulou, Tamas Lazar, Bjorn Menten, Julia Orkin, Simon Sadedin, Meaghan Snell, Arnaud Vanlander, Sarah Vergult, Susan M White, Stephen W Scherer, Robin Z Hayeems, Susan Blaser, Shoshana J Wodak, David Chitayat, Christian R Marshall Show all

GENETICS IN MEDICINE | NATURE PUBLISHING GROUP | Published : 2019

Abstract

PURPOSE: RAC3 is an underexamined member of the Rho GTPase gene family that is expressed in the developing brain and linked to key cellular functions. De novo missense variants in the homolog RAC1 were recently associated with developmental disorders. In the RAC subfamily, transforming missense changes at certain shared residues have been observed in human cancers and previously characterized in experimental studies. The purpose of this study was to determine whether constitutional dysregulation of RAC3 is associated with human disease. METHODS: We discovered a RAC3 variant in the index case using genome sequencing, and searched for additional variants using international data-sharing initia..

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Grants

Funding Acknowledgements

The research conducted at The Hospital for Sick Children was funded by the Norm Saunders Complex Care Initiative, the Centre for Genetic Medicine, the Centre for Applied Genomics, the Hospital for Sick Children, Genome Canada, and the University of Toronto McLaughlin Centre. B.C. is a senior clinical investigator of the Research Foundation-Flanders. Funding for the UDP-Vic was provided by philanthropic donation and the Murdoch Children's Research Institute. The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. The funding bodies played no role in the design of the study, the collection, analysis, and interpretation of data, or the writing of the manuscript.