Title: A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling
Authors: Wieczorek, Dagmar ×
Bögershausen, Nina
Beleggia, Filippo
Steiner-Haldenstätt, Sabine
Pohl, Esther
Li, Yun
Milz, Esther
Martin, Marcel
Thiele, Holger
Altmüller, Janine
Alanay, Yasemin
Kayserili, Hülya
Klein-Hitpass, Ludger
Böhringer, Stefan
Wollstein, Andreas
Albrecht, Beate
Boduroglu, Koray
Caliebe, Almuth
Chrzanowska, Krystyna
Cogulu, Ozgur
Cristofoli, Francesca
Czeschik, Johanna Christina
Devriendt, Koenraad
Dotti, Maria Teresa
Elcioglu, Nursel
Gener, Blanca
Goecke, Timm O
Krajewska-Walasek, Malgorzata
Guillén-Navarro, Encarnación
Hayek, Joussef
Houge, Gunnar
Kilic, Esra
Simsek-Kiper, Pelin Özlem
López-González, Vanesa
Kuechler, Alma
Lyonnet, Stanislas
Mari, Francesca
Marozza, Annabella
Mathieu Dramard, Michèle
Mikat, Barbara
Morin, Gilles
Morice-Picard, Fanny
Ozkynay, Ferda
Rauch, Anita
Renieri, Alessandra
Tinschert, Sigrid
Utine, G Eda
Vilain, Catheline
Vivarelli, Rossella
Zweier, Christiane
Nürnberg, Peter
Rahmann, Sven
Vermeesch, Joris
Lüdecke, Hermann-Josef
Zeschnigk, Michael
Wollnik, Bernd #
Issue Date: Dec-2013
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:22 issue:25 pages:5121-35
Abstract: Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategies.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
Wieczorek.pdfpublisher's version pdf Published 17220KbAdobe PDFView/Open Request a copy

These files are only available to some KU Leuven Association staff members


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science