English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction

Braunholz, D., Hullings, M., Gil-Rodriguez, M. C., Fincher, C. T., Mallozzi, M. B., Loy, E., et al. (2012). Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction. European journal og human genetics: EJHG; the official journal of the European Society of Human Genetics, 20(3), 271-276. doi:10.1038/ejhg.2011.175.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-EC66-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-EC67-8
Genre: Journal Article

Files

show Files
hide Files
:
Braunholz.pdf (Publisher version), 459KB
Name:
Braunholz.pdf
Description:
Corrected online: 16 February 2012
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2012 European Society of Human Genetics
License:
-

Locators

show

Creators

show
hide
 Creators:
Braunholz, D., Author
Hullings, M., Author
Gil-Rodriguez, M. C., Author
Fincher, C. T., Author
Mallozzi, M. B., Author
Loy, E., Author
Albrecht, M., Author
Kaur, M., Author
Limon, J., Author
Rampuria, A., Author
Clark, D., Author
Kline, A., Author
Dalski, A., Author
Eckhold, J., Author
Tzschach, A.1, Author              
Hennekam, R., Author
Gillessen-Kaesbach, G., Author
Wierzba, J., Author
Krantz, I. D., Author
Deardorff, M. A., Author
Kaiser, F. J., 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              

Content

show
hide
Free keywords: De Lange Syndrome/*genetics/*metabolism Facies Humans Intercellular Signaling Peptides and Proteins/chemistry/*metabolism *Mutation, Missense Phenotype Protein Binding/genetics Protein Interaction Domains and Motifs Proteins/*genetics
 Abstract: Cornelia de Lange syndrome (CdLS; or Brachmann-de Lange syndrome) is a dominantly inherited congenital malformation disorder with features that include characteristic facies, cognitive delays, growth retardation and limb anomalies. Mutations in nearly 60% of CdLS patients have been identified in NIPBL, which encodes a regulator of the sister chromatid cohesion complex. NIPBL, also known as delangin, is a homolog of yeast and amphibian Scc2 and C. elegans PQN-85. Although the exact mechanism of NIPBL function in sister chromatid cohesion is unclear, in vivo yeast and C. elegans experiments and in vitro vertebrate cell experiments have demonstrated that NIPBL/Scc2 functionally interacts with the MAU2/Scc4 protein to initiate loading of cohesin onto chromatin. To test the significance of this model in the clinical setting of CdLS, we fine-mapped the NIBPL-MAU2 interaction domain and tested the functional significance of missense mutations and variants in NIPBL and MAU2 identified in these minimal domains in a cohort of patients with CdLS. We demonstrate that specific novel mutations at the N-terminus of the MAU2-interacting domain of NIBPL result in markedly reduced MAU2 binding, although we appreciate no consistent clinical difference in the small group of patients with these mutations. These data suggest that factors in addition to MAU2 are essential in determining the clinical features and severity of CdLS.

Details

show
hide
Language(s): eng - English
 Dates: 2012-02-162012
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1038/ejhg.2011.175
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: European journal og human genetics : EJHG ; the official journal of the European Society of Human Genetics
  Other : Eur J Hum Genet
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Basel : Karger
Pages: - Volume / Issue: 20 (3) Sequence Number: - Start / End Page: 271 - 276 Identifier: ISSN: 1018-4813
CoNE: https://pure.mpg.de/cone/journals/resource/954925585277_2