Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.
Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.
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RFX家族转录因子的干扰会导致自闭症、注意力缺陷/多动障碍、智力残疾和行为失调。
DOI：
10.1038/s41436-021-01114-z
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发表时间：
2021-06
影响因子：
8.8
通讯作者：
Yu, Timothy W.
中科院分区：
文献类型：
--
作者：
Harris, Holly K.;Nakayama, Tojo;Lai, Jenny;Zhao, Boxun;Argyrou, Nikoleta;Gubbels, Cynthia S.;Soucy, Aubrie;Genetti, Casie A.;Suslovitch, Victoria;Rodan, Lance H.;Tiller, George E.;Lesca, Gaetan;Gripp, Karen W.;Asadollahi, Reza;Hamosh, Ada;Applegate, Carolyn D.;Turnpenny, Peter D.;Simon, Marleen E. H.;Volker-Touw, Catharina M. L.;van Gassen, Koen L. I.;van Binsbergen, Ellen;Pfundt, Rolph;Gardeitchik, Thatjana;de Vries, Bert B. A.;Immken, LaDonna L.;Buchanan, Catherine;Willing, Marcia;Toler, Tomi L.;Fassi, Emily;Baker, Laura;Vansenne, Fleur;Wang, Xiadong;Ambrus, Julian L., Jr.;Fannemel, Madeleine;Posey, Jennifer E.;Agolini, Emanuele;Novelli, Antonio;Rauch, Anita;Boonsawat, Paranchai;Fagerberg, Christina R.;Larsen, Martin J.;Kibaek, Maria;Labalme, Audrey;Poisson, Alice;Payne, Katelyn K.;Walsh, Laurence E.;Aldinger, Kimberly A.;Balciuniene, Jorune;Skraban, Cara;Gray, Christopher;Murrell, Jill;Bupp, Caleb P.;Pascolini, Giulia;Grammatico, Paola;Broly, Martin;Kury, Sebastien;Nizon, Mathilde;Rasool, Iqra Ghulam;Zahoor, Muhammad Yasir;Kraus, Cornelia;Reis, Andre;Iqbal, Muhammad;Uguen, Kevin;Audebert-Bellanger, Severine;Ferec, Claude;Redon, Sylvia;Baker, Janice;Wu, Yunhong;Zampino, Guiseppe;Syrbe, Steffan;Brosse, Ines;Jamra, Rami Abou;Dobyns, William B.;Cohen, Lilian L.;Blomhoff, Anne;Mignot, Cyril;Keren, Boris;Courtin, Thomas;Agrawal, Pankaj B.;Beggs, Alan H.;Yu, Timothy W.
我们描述了一种新的神经行为表型自闭症谱系障碍，智力残疾，和/或注意力缺陷/多动障碍与从头或遗传有害的RFX基因家族成员的变异。RFX基因是进化上保守的转录因子，作为中枢神经系统发育和纤毛发生的主要调节因子。我们收集了一组38名个体（来自33个不相关的家庭）与RFX 3，RFX 4和RFX 7的新发变异。我们描述了它们常见的临床表型，并对这些基因的表达模式和下游靶点进行了生物信息学分析，因为它们与其他神经发育风险基因有关。这些个体具有共同的神经行为特征，包括自闭症谱系障碍（ASD），智力残疾和/或注意力缺陷/多动障碍（ADHD）;其他常见的特征包括对感官刺激的超敏反应和睡眠问题。RFX 3、RFX 4和RFX 7在发育和成年人脑中强烈表达，并且X盒结合基序以及RFX ChIP-seq峰在已知ASD风险基因的顺式调节区域中富集。这些结果确立了RFX 3、RFX 4和RFX 7在单基因智力残疾、ADHD和ASD病例中的有害变异的可能作用，并将这些基因定位为与神经发育疾病发病机制相关的神经生物学通路的潜在关键转录调节因子。
We describe a novel neurobehavioral phenotype of autism spectrum disorder, intellectual disability, and/or attention deficit/hyperactivity disorder associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. These individuals share neurobehavioral features including autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD); other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
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影响因子：
6.4
作者：
Banaschewski, Tobias;Becker, Katja;Scherag, Susann;Franke, Barbara;Coghill, David
通讯作者：
Coghill, David
影响因子：
30.8
作者：
Krumm, Niklas;Turner, Tychele N.;Baker, Carl;Vives, Laura;Mohajeri, Kiana;Witherspoon, Kali;Raja, Archana;Coe, Bradley P.;Stessman, Holly A.;He, Zong-Xiao;Leal, Suzanne M.;Bernier, Raphael;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
30.8
作者：
Coe, Bradley P.;Stessman, Holly A. F.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.