MedElevator Войти в исследования
← Поиск публикаций

DOI 10.1126/sciadv.aax2166

Медицинская библиотека · Science advances · 2019

Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission.

Guo Hui, Li Ying, Shen Lu, Wang Tianyun, Jia Xiangbin, Liu Lijuan, Xu Tao, Ou Mengzhu, Hoekzema Kendra, Wu Huidan, Gillentine Madelyn A, Liu Cenying, Ni Hailun, Peng Pengwei, Zhao Rongjuan, Zhang Yu, Phornphutkul Chanika, Stegmann Alexander P A, Prada Carlos E, Hopkin Robert J, Shieh Joseph T, McWalter Kirsty, Monaghan Kristin G, van Hasselt Peter M, van Gassen Koen, Bai Ting, Long Min, Han Lin, Quan Yingting, Chen Meilin, Zhang Yaowen, Li Kuokuo, Zhang Qiumeng, Tan Jieqiong, Zhu Tengfei, Liu Yaning, Pang Nan, Peng Jing, Scott Daryl A, Lalani Seema R, Azamian Mahshid, Mancini Grazia M S, Adams Darius J, Kvarnung Malin, Lindstrand Anna, Nordgren Ann, Pevsner Jonathan, Osei-Owusu Ikeoluwa A, Romano Corrado, Calabrese Giuseppe, Galesi Ornella, Gecz Jozef, Haan Eric, Ranells Judith, Racobaldo Melissa, Nordenskjold Magnus, Madan-Khetarpal Suneeta, Sebastian Jessica, Ball Susie, Zou Xiaobing, Zhao Jingping, Hu Zhengmao, Xia Fan, Liu Pengfei, Rosenfeld Jill A, de Vries Bert B A, Bernier Raphael A, Xu Zhi-Qing David, Li Honghui, Xie Wei, Hufnagel Robert B, Eichler Evan E, Xia Kun

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neurodevelopmental and neuropsychiatric disorders. Here, we report a significant burden of heterozygous, likely gene-disrupting variants in CSDE1 (encoding a highly constrained RNA binding protein) among patients with autism and related neurodevelopmental disabilities. Analysis of 17 patients identifies common phenotypes including autism, intellectual disability, language and motor delay, seizures, macrocephaly, and variable ocular abnormalities. HITS-CLIP revealed that Csde1-binding targets are enriched in autism-associated gene sets, especially FMRP targets, and in neuronal development and synaptic plasticity-related pathways. Csde1 knockdown in primary mouse cortical neurons leads to an overgrowth of the neurites and abnormal dendritic spine morphology/synapse formation and impaired synaptic transmission, whereas mutant and knockdown experiments in Drosophila result in defects in synapse growth and synaptic transmission. Our study defines a new autism-related syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.

Для цитирования: Guo Hui, Li Ying, Shen Lu, Wang Tianyun, Jia Xiangbin, Liu Lijuan, Xu Tao, Ou Mengzhu, Hoekzema Kendra, Wu Huidan, Gillentine Madelyn A, Liu Cenying, Ni Hailun, Peng Pengwei, Zhao Rongjuan, Zhang Yu, Phornphutkul Chanika, Stegmann Alexander P A, Prada Carlos E, Hopkin Robert J, Shieh Joseph T, McWalter Kirsty, Monaghan Kristin G, van Hasselt Peter M, van Gassen Koen, Bai Ting, Long Min, Han Lin, Quan Yingting, Chen Meilin, Zhang Yaowen, Li Kuokuo, Zhang Qiumeng, Tan Jieqiong, Zhu Tengfei, Liu Yaning, Pang Nan, Peng Jing, Scott Daryl A, Lalani Seema R, Azamian Mahshid, Mancini Grazia M S, Adams Darius J, Kvarnung Malin, Lindstrand Anna, Nordgren Ann, Pevsner Jonathan, Osei-Owusu Ikeoluwa A, Romano Corrado, Calabrese Giuseppe, Galesi Ornella, Gecz Jozef, Haan Eric, Ranells Judith, Racobaldo Melissa, Nordenskjold Magnus, Madan-Khetarpal Suneeta, Sebastian Jessica, Ball Susie, Zou Xiaobing, Zhao Jingping, Hu Zhengmao, Xia Fan, Liu Pengfei, Rosenfeld Jill A, de Vries Bert B A, Bernier Raphael A, Xu Zhi-Qing David, Li Honghui, Xie Wei, Hufnagel Robert B, Eichler Evan E, Xia Kun. Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission.. Science advances. 2019. DOI: 10.1126/sciadv.aax2166.

Предметные рубрики MeSH

AdolescentAnimalsAutistic DisorderChildChild, PreschoolDNA-Binding ProteinsDisease Models, AnimalFemaleGenetic Association StudiesGenetic LociGenetic Predisposition to DiseaseGenetic VariationHumansMaleMiceNeurogenesisNeuronsPedigreePhenotypeRNA-Binding ProteinsSynapsesSynaptic TransmissionYoung Adult
Подготовка и перевод публикации
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.

Тип публикации указан по данным источника. Уровень доказательности автоматически не присваивается.