| TAN, Tiong Yang, Jiří SEDMÍK, Mark P. FITZGERALD, Rivka SUKENIK HALEVY, Liam KEEGAN, Ingo HELBIG, Lina BASEL-SALMON, Lior COHEN, Rachel STRAUSSBERG, Wendy K. CHUNG, Mayada HELAL, Reza MAROOFIAN, Henry HOULDEN, Jane JUUSOLA, Simon SADEDIN, Lynn PAIS, Katherine B. HOWELL, Susan M. WHITE, John CHRISTODOULOU a Mary Anne O'CONNELL. Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures. The American Journal of Human Genetics. University of Chicago Press for the American Society of Human Genetics, 2020, roč. 106, č. 4, s. 467-483. ISSN 0002-9297. Dostupné z: https://dx.doi.org/10.1016/j.ajhg.2020.02.015. |
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@article{1639636,
author = {Tan, Tiong Yang and Sedmík, Jiří and Fitzgerald, Mark P. and Sukenik Halevy, Rivka and Keegan, Liam and Helbig, Ingo and BaselandSalmon, Lina and Cohen, Lior and Straussberg, Rachel and Chung, Wendy K. and Helal, Mayada and Maroofian, Reza and Houlden, Henry and Juusola, Jane and Sadedin, Simon and Pais, Lynn and Howell, Katherine B. and White, Susan M. and Christodoulou, John and O'Connell, Mary Anne},
article_number = {4},
doi = {http://dx.doi.org/10.1016/j.ajhg.2020.02.015},
keywords = {ADAR2; microcephaly; migrating focal seizures; epilepsy; intellectual disability; RNA editing},
language = {eng},
issn = {0002-9297},
journal = {The American Journal of Human Genetics},
title = {Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures},
url = {https://www.cell.com/ajhg/pdf/S0002-9297(20)30057-4.pdf},
volume = {106},
year = {2020}
}
TY - JOUR
ID - 1639636
AU - Tan, Tiong Yang - Sedmík, Jiří - Fitzgerald, Mark P. - Sukenik Halevy, Rivka - Keegan, Liam - Helbig, Ingo - Basel-Salmon, Lina - Cohen, Lior - Straussberg, Rachel - Chung, Wendy K. - Helal, Mayada - Maroofian, Reza - Houlden, Henry - Juusola, Jane - Sadedin, Simon - Pais, Lynn - Howell, Katherine B. - White, Susan M. - Christodoulou, John - O'Connell, Mary Anne
PY - 2020
TI - Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures
JF - The American Journal of Human Genetics
VL - 106
IS - 4
SP - 467-483
EP - 467-483
PB - University of Chicago Press for the American Society of Human Genetics
SN - 00029297
KW - ADAR2
KW - microcephaly
KW - migrating focal seizures
KW - epilepsy
KW - intellectual disability
KW - RNA editing
UR - https://www.cell.com/ajhg/pdf/S0002-9297(20)30057-4.pdf
N2 - 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 derived from one of the individuals. We demonstrate that these ADAR2 variants lead to reduced editing activity on a known ADAR2 substrate. We also demonstrate that one variant leads to changes in splicing of ADARB1 transcript isoforms. These findings reinforce the importance of RNA editing in brain development and introduce ADARB1 as a genetic etiology in individuals with intellectual disability, microcephaly, and epilepsy.
ER -
TAN, Tiong Yang, Jiří SEDMÍK, Mark P. FITZGERALD, Rivka SUKENIK HALEVY, Liam KEEGAN, Ingo HELBIG, Lina BASEL-SALMON, Lior COHEN, Rachel STRAUSSBERG, Wendy K. CHUNG, Mayada HELAL, Reza MAROOFIAN, Henry HOULDEN, Jane JUUSOLA, Simon SADEDIN, Lynn PAIS, Katherine B. HOWELL, Susan M. WHITE, John CHRISTODOULOU a Mary Anne O'CONNELL. Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures. \textit{The American Journal of Human Genetics}. University of Chicago Press for the American Society of Human Genetics, 2020, roč.~106, č.~4, s.~467-483. ISSN~0002-9297. Dostupné z: https://dx.doi.org/10.1016/j.ajhg.2020.02.015.
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