English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Translocations Disrupting PHF21A in the Potocki-Shaffer-Syndrome Region Are Associated with Intellectual Disability and Craniofacial Anomalies

Kim, H.-G., Kim, H. T., Leach, N. T., Lan, F., Ullmann, R., Silahtaroglu, A., et al. (2012). Translocations Disrupting PHF21A in the Potocki-Shaffer-Syndrome Region Are Associated with Intellectual Disability and Craniofacial Anomalies. The American Journal of Human Genetics, 91(1), 56-72. doi:10.1016/j.ajhg.2012.05.005.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-EC76-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-EC77-4
Genre: Journal Article

Files

show Files
hide Files
:
Kim.pdf (Publisher version), 2MB
Name:
Kim.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2012 The American Society of Human Genetics
License:
-

Locators

show

Creators

show
hide
 Creators:
Kim, H.-G.1, Author              
Kim, H. T., Author
Leach, N. T., Author
Lan, F., Author
Ullmann, R.2, Author              
Silahtaroglu, A., Author
Kurth, I., Author
Nowka, A., Author
Seong, I. S., Author
Shen, Y., Author
Talkowski, M. E., Author
Ruderfer, D., Author
Lee, J. H., Author
Glotzbach, C., Author
Ha, K., Author
Kjaergaard, S., Author
Levin, A. V., Author
Romeike, B. F., Author
Kleefstra, T., Author
Bartsch, O., Author
Elsea, S. H., AuthorJabs, E. W., AuthorMacdonald, M. E., AuthorHarris, D. J., AuthorQuade, B. J., AuthorRopers, H.-H.1, Author              Shaffer, L. G., AuthorKutsche, K., AuthorLayman, L. C., AuthorTommerup, N., AuthorKalscheuer, V. M.3, Author              Shi, Y., AuthorMorton, C. C., AuthorKim, C. H., AuthorGusella, J. F., Author more..
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1433549              
2Molecular Cytogenetics (Reinhard Ullmann), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479645              
3Chromosome Rearrangements and Disease (Vera Kalscheuer), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479642              

Content

show
hide
Free keywords: -
 Abstract: 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.

Details

show
hide
Language(s): eng - English
 Dates: 2012-07-052012-07-13
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.ajhg.2012.05.005
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: The American Journal of Human Genetics
  Other : Am. J. Hum. Genet.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: American Society of Human Genetics
Pages: - Volume / Issue: 91 (1) Sequence Number: - Start / End Page: 56 - 72 Identifier: ISSN: 0002-9297
CoNE: /journals/resource/954925377893_1