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  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.

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Corrected online: 16 February 2012
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© 2012 European Society of Human Genetics
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 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              

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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.

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Language(s): eng - English
 Dates: 2012-02-162012
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/ejhg.2011.175
 Degree: -

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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
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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