De novo ATP1A3 variants cause polymicrogyria
| العنوان: | De novo ATP1A3 variants cause polymicrogyria |
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| المؤلفون: | Nina Ekhilevitch, Takeshi Mizuguchi, Kazuyuki Nakamura, Masami Togawa, Kazuhiro Ogata, Naomichi Matsumoto, Asako Horino, Hirotomo Saitsu, Yukihiro Ikeda, Mai Satoh, Goni Merhav, Yasunari Sakai, Momoko Sasazuki, Fumiaki Tanaka, Hiroyuki Torisu, Hidehisa Takahashi, Hiroshi Doi, Toshiro Hara, Mazumi Miura, Takuma Kumamoto, Shouichi Ohga, Chiaki Ohtaka-Maruyama, Atsushi Takata, Takabumi Miyama, Mitsuhiro Kato, Masataka Fukuoka, Hideyuki Asai, Hideyuki Takeuchi, Tatsuhiko Tsunoda, Hiroko Ikeda, Takaaki Matsui, Atsushi Suzuki, Yushi Noguchi, Nobusuke Kimura, Keisuke Hamada, Mitsuko Nakashima, Eriko Koshimizu, Fuyuki Miya, Kohei Hamanaka, Noriko Miyake, Satoko Miyatake, Nodoka Hinokuma, Tomonori Hirose, Yoko Nishimura, Akio Yamashita, Kaoru Amemiya, Masaki Miura, Yuri Sonoda, Kazunori Sasaki |
| المصدر: | Science Advances |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Pes cavus, Pathology, medicine.medical_specialty, Pathogenesis, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, ATP1A3, Polymicrogyria, medicine, Genetics, Research Articles, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Cerebellar ataxia, business.industry, Alternating hemiplegia of childhood, SciAdv r-articles, medicine.disease, medicine.anatomical_structure, Cerebral cortex, medicine.symptom, business, 030217 neurology & neurosurgery, Research Article |
| الوصف: | ATP1A3, a mutated gene for AHC, RDP, and CAPOS, is also associated with polymicrogyria by different functional variants. Polymicrogyria is a common malformation of cortical development whose etiology remains elusive. We conducted whole-exome sequencing for 124 patients with polymicrogyria and identified de novo ATP1A3 variants in eight patients. Mutated ATP1A3 causes functional brain diseases, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorineural deafness (CAPOS). However, our patients showed no clinical features of AHC, RDP, or CAPOS and had a completely different phenotype: a severe form of polymicrogyria with epilepsy and developmental delay. Detected variants had different locations in ATP1A3 and different functional properties compared with AHC-, RDP-, or CAPOS-associated variants. In the developing cerebral cortex of mice, radial neuronal migration was impaired in neurons overexpressing the ATP1A3 variant of the most severe patients, suggesting that this variant is involved in cortical malformation pathogenesis. We propose a previously unidentified category of polymicrogyria associated with ATP1A3 abnormalities. |
| تدمد: | 2375-2548 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc4dd8c88e7b79b40aba184601669682 https://pubmed.ncbi.nlm.nih.gov/33762331 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fc4dd8c88e7b79b40aba184601669682 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23752548 |
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