Journal article
Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures
TY Tan, J Sedmík, MP Fitzgerald, RS Halevy, LP Keegan, I Helbig, L Basel-Salmon, L Cohen, R Straussberg, WK Chung, M Helal, R Maroofian, H Houlden, J Juusola, S Sadedin, L Pais, KB Howell, SM White, J Christodoulou, MA O'Connell
American Journal of Human Genetics | CELL PRESS | Published : 2020
Abstract
The RNA editing enzyme ADAR2 is essential for the recoding of brain transcripts. Impaired ADAR2 editing leads to early-onset epilepsy and premature death in a mouse model. Here, we report bi-allelic variants in ADARB1, the gene encoding ADAR2, in four unrelated individuals with microcephaly, intellectual disability, and epilepsy. In one individual, a homozygous variant in one of the double-stranded RNA-binding domains (dsRBDs) was identified. In the others, variants were situated in or around the deaminase domain. To evaluate the effects of these variants on ADAR2 enzymatic activity, we performed in vitro assays with recombinant proteins in HEK293T cells and ex vivo assays with fibroblasts d..
View full abstractGrants
Awarded by National Heart, Lung, and Blood Institute
Funding Acknowledgements
We acknowledge the Core Facility Cellular Imaging (CELLIM) of Central European Institute of Technology (CEITEC) supported by the Czech-BioImaging large RI project (LM2015062 funded by the Ministry of Education Youth and Sports Czech Republic (MEYS CR)), for support with obtaining scientific data presented in this paper. W.K.C. was funded by grants from the Simons Foundation Autism Research Initiative (SFARI) and the JPB Foundation. This work was supported by the European Union's Seventh Framework Programme for research, technological development, and demonstration under grant agreement number 621368 to M.A.O. L.P.K. has received funding from Czech Science Foundation project number 19-16963S. The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. Sequencing and analysis of individual 1 were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and were funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung, and Blood Institute under grant UM1 HG008900 to Daniel MacArthur and Heidi Rehm.