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Autor
Basel-Salmon, Lina 1 Christodoulou, John 1 Chung, Wendy K 1 Cohen, Lior 1 Fitzgerald, Mark P 1 Halevy, Rivka Sukenik 1 Helal, Mayada 1 Helbig, Ingo 1 Houlden, Henry 1 Howell, Katherine B 1 Juusola, Jane 1 Keegan, Liam P 1 Maroofian, Reza 1 O'Connell, Mary A 1 Pais, Lynn 1 Sadedin, Simon 1 Sedmík, Jiří 1 Straussberg, Rachel 1 Tan, Tiong Yang 1 White, Susan M 1
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Pracoviště
Broad Center for Mendelian Genomics B... 1 Central European Institute of Technol... 1 Department of Neurology Royal Childre... 1 Department of Neuromuscular Disorders... 1 Department of Pediatrics Columbia Uni... 1 Department of Pediatrics University o... 1 Division of Neurology Departments of ... 1 Felsenstein Medical Research Center P... 1 GeneDx Gaithersburg MD 20877 USA 1 Murdoch Children's Research Institute... 1 Pediatric Genetics Unit Schneider Chi... 1 Pediatric Neurology Unit Schneider Ch... 1 Raphael Recanati Genetic Institute Ra... 1 Sackler Faculty of Medicine Tel Aviv ... 1 The Epilepsy NeuroGenetics Initiative... 1 Victorian Clinical Genetics Services ... 1
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Autor
Basel-Salmon, Lina 1 Christodoulou, John 1 Chung, Wendy K 1 Cohen, Lior 1 Fitzgerald, Mark P 1 Halevy, Rivka Sukenik 1 Helal, Mayada 1 Helbig, Ingo 1 Houlden, Henry 1 Howell, Katherine B 1 Juusola, Jane 1 Keegan, Liam P 1 Maroofian, Reza 1 O'Connell, Mary A 1 Pais, Lynn 1 Sadedin, Simon 1 Sedmík, Jiří 1 Straussberg, Rachel 1 Tan, Tiong Yang 1 White, Susan M 1
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Pracoviště
Broad Center for Mendelian Genomics B... 1 Central European Institute of Technol... 1 Department of Neurology Royal Childre... 1 Department of Neuromuscular Disorders... 1 Department of Pediatrics Columbia Uni... 1 Department of Pediatrics University o... 1 Division of Neurology Departments of ... 1 Felsenstein Medical Research Center P... 1 GeneDx Gaithersburg MD 20877 USA 1 Murdoch Children's Research Institute... 1 Pediatric Genetics Unit Schneider Chi... 1 Pediatric Neurology Unit Schneider Ch... 1 Raphael Recanati Genetic Institute Ra... 1 Sackler Faculty of Medicine Tel Aviv ... 1 The Epilepsy NeuroGenetics Initiative... 1 Victorian Clinical Genetics Services ... 1
- Formát
- Publikační typ
- Check Tag
- Kategorie
- Jazyk
- Země
- Časopis/zdroj
- Dostupnost
- Vlastník
- Tan, Tiong Yang
- Sedmík, Jiří
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Fitzgerald, Mark P
Autor Fitzgerald, Mark P Division of Neurology, Departments of Neurology and Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA The Epilepsy NeuroGenetics Initiative, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
- Halevy, Rivka Sukenik
- Keegan, Liam P
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Helbig, Ingo
Autor Helbig, Ingo Division of Neurology, Departments of Neurology and Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA The Epilepsy NeuroGenetics Initiative, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
- Basel-Salmon, Lina
- Cohen, Lior
- Straussberg, Rachel
- Chung, Wendy K
NLK
Cell Press Free Archives
od 1997-01-01 do Před 6 měsíci
Free Medical Journals
od 1949 do Před 6 měsíci
PubMed Central
od 1949 do Před 6 měsíci
Europe PubMed Central
od 1949 do Před 6 měsíci
Open Access Digital Library
od 2005-01-01
Elsevier Open Access Journals
od 1997-06-01
Elsevier Open Archive Journals
od 1997 do Před 6 měsíci
PubMed
32220291
DOI
10.1016/j.ajhg.2020.02.015
Knihovny.cz E-zdroje
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.
- MeSH
- adenosindeaminasa genetika MeSH
- alely MeSH
- alternativní sestřih genetika MeSH
- dítě MeSH
- genetická predispozice k nemoci genetika MeSH
- genetická variace genetika MeSH
- HEK293 buňky MeSH
- lidé MeSH
- mentální retardace genetika MeSH
- mikrocefalie genetika MeSH
- předškolní dítě MeSH
- proteiny vázající RNA genetika MeSH
- sestřih RNA genetika MeSH
- záchvaty genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
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