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Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies 期刊论文

编号：

25dfc199-99fc-4606-b8f6-92ca75f068b5
作者：

Kim, Hyunggoo[0]^[1] Kim, Hyuntaek[1]^[2] Leach, Natalia Tszine[2]^[3] Lan, Fei[3]^[4] Ullmann, Reinhard[4]^[5] Asli Silahtaroglu, undefined[5]^[6] Kurth, Ingo[6]^[7] Nowka, Anja[7]^[8] Seong, Ihnsik[8]^[9] Shen, Yiping[9]^[10] Talkowski, Michael E.[10]^[11] Ruderfer, Douglas M.[11]^[12] Lee, Jihyun[12]^[13] Glotzbach, Caron D.[13]^[14] Ha, Kyungsoo[14]^[15] Kj?rgaard, Susanne[15]^[16] Levin, Alex V.[16]^[17] Romeike, Bernd F.M.[17]^[18] Kleefstra, Tjitske[18]^[19] Bartsch, Oliver[19]^[20] Elsea, Sarah H.[20]^[21] Jabs, Ethylin Wang[21]^[22] MacDonald, Marcy E.[22]^[23] Harris, David J.[23]^[24] Quade, Bradley J.[24]^[25] Ropers, Hans Hilger[25]^[5] Shaffer, Lisa G.[26]^[26] Kutsche, Kerstin[27]^[27] Layman, Lawrence C.[28]^[28] Tommerup, Niels Rath[29]^[6] Kalscheuer, Vera M.[30]^[29] Shi, Yang[31]^[30] Morton, Cynthia Casson[32]^[25] Kim, Cheolhee[33]^[2] Gusella, James F.[34]^[23]
地址：

[1]Medical College of Georgia, Department of Neuroscience and Regenerative Medicine,Augusta,United States
[2]Chungnam National University, Department of Biology,Daejeon,South Korea
[3],Boston,United States
[4]Fudan University Shanghai Medical College, Epigenetics Laboratory,Shanghai,China
[5]Max Planck Institute for Molecular Genetics,Berlin,Germany
[6]Kobenhavns Universitet, Center for non-coding RNA in Technology and Health,Copenhagen,Denmark
[7]Friedrich Schiller Universitat Jena, Institute of Human Genetics,Jena,Germany
[8]Max Planck Institute for Molecular Genetics, Otto Warburg Laboratory,Berlin,Germany
[9]Massachusetts General Hospital, Molecular Neurogenetics Unit,Boston,United States
[10]Massachusetts General Hospital, Department of Neurology,Boston,United States
[11]Massachusetts General Hospital, Department of Neurology and Center for Aging,Boston,United States
[12]Icahn School of Medicine at Mount Sinai, Friedman Brain Institute and Department of Psychiatry,New York,United States
[13]Massachusetts General Hospital and Harvard Medical School, Molecular Neurogenetics Laboratory,Boston,United States
[14]Signature Genomic Laboratories,Spokane,United States
[15]Osong Medical Innovation Foundation, New Drug Development Center,Cheongju,South Korea
[16]Copenhagen University Hospital, Chromosome Laboratory,Copenhagen,Denmark
[17]Thomas Jefferson University, Pediatric Ophthalmology and Ocular Genetics,Philadelphia,United States
[18]Universitatsklinikum Jena und Medizinische Fakultat, Department of Pathology,Jena,Germany
[19]Radboud University Nijmegen Medical Centre, Department of Human Genetics,Nijmegen,Netherlands
[20]s Hospital, Department of Medical Genetics,Chattanooga,United States
[21]Baylor College of Medicine, Department of Molecular and Human Genetics,Houston,United States
[22]The Johns Hopkins School of Medicine, Department of Pediatrics,Baltimore,United States
[23]Massachusetts General Hospital, Center for Human Genetic Research,Boston,United States
[24]s Hospital Boston, Division of Genetics and Genomics,Boston,United States
[25]s Hospital, Department of Pathology,Boston,United States
[26]Genetic Veterinary Sciences, Inc., Paw Print Genetics,Spokane,United States
[27]Universitatsklinikum Hamburg-Eppendorf und Medizinische Fakultat,Hamburg,Germany
[28]Augusta University, Department of Obstetrics and Gynecology,Augusta,United States
[29]Max Planck Institute for Molecular Genetics, Research Group Development and Disease,Berlin,Germany
[30]Harvard Medical School, Department of Cell Biology,Boston,United States
语种：

英文
期刊：

American Journal of Human Genetics ISSN：0002-9297 2012 年 91 卷 1 期 (56 - 72)
收录：
摘要：

Potocki-Shaffer syndrome (PSS) is a contiguous gene disorder due to the interstitial deletion of band p11.2 of chromosome 11 and is characterized by multiple exostoses, parietal foramina, intellectual disability (ID), and craniofacial anomalies (CFAs). Despite the identification of individual genes responsible for multiple exostoses and parietal foramina in PSS, the identity of the gene(s) associated with the ID and CFA phenotypes has remained elusive. Through characterization of independent subjects with balanced translocations and supportive comparative deletion mapping of PSS subjects, we have uncovered evidence that the ID and CFA phenotypes are both caused by haploinsufficiency of a single gene, PHF21A, at 11p11.2. PHF21A encodes a plant homeodomain finger protein whose murine and zebrafish orthologs are both expressed in a manner consistent with a function in neurofacial and craniofacial development, and suppression of the latter led to both craniofacial abnormalities and neuronal apoptosis. Along with lysine-specific demethylase 1 (LSD1), PHF21A, also known as BHC80, is a component of the BRAF-histone deacetylase complex that represses target-gene transcription. In lymphoblastoid cell lines from two translocation subjects in whom PHF21A was directly disrupted by the respective breakpoints, we observed derepression of the neuronal gene SCN3A and reduced LSD1 occupancy at the SCN3A promoter, supporting a direct functional consequence of PHF21A haploinsufficiency on transcriptional regulation. Our finding that disruption of PHF21A by translocations in the PSS region is associated with ID adds to the growing list of ID-associated genes that emphasize the critical role of transcriptional regulation and chromatin remodeling in normal brain development and cognitive function. © 2012 The American Society of Human Genetics.
推荐引用方式
GB/T 7714：

Kim Hyunggoo/55766544300[0],Kim Hyuntaek/36183224700[1],Leach Natalia Tszine/6701636722[2], et al. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies [J].American Journal of Human Genetics,2012,91(1):56-72.
APA：

Kim Hyunggoo/55766544300[0],Kim Hyuntaek/36183224700[1],Leach Natalia Tszine/6701636722[2],Lan Fei/8969841200[3],&Gusella James F./36065462700[34].(2012).Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies .American Journal of Human Genetics,91(1):56-72.
MLA：

Kim Hyunggoo/55766544300[0], et al. "Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies" .American Journal of Human Genetics 91,1(2012):56-72.

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