A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

dc.contributor.authorWieczorek, Dagmar
dc.contributor.authorBoegershausen, Nina
dc.contributor.authorBeleggia, Filippo
dc.contributor.authorSteiner-Haldenstaett, Sabine
dc.contributor.authorPohl, Esther
dc.contributor.authorLi, Yun
dc.contributor.authorMilz, Esther
dc.contributor.authorMartin, Marcel
dc.contributor.authorThiele, Holger
dc.contributor.authorAltmueller, Janine
dc.contributor.authorAlanay, Yasemin
dc.contributor.authorKayserili, Hulya
dc.contributor.authorKlein-Hitpass, Ludger
dc.contributor.authorBohringer, Stefan
dc.contributor.authorWollstein, Andreas
dc.contributor.authorAlbrecht, Beate
dc.contributor.authorBoduroglu, Koray
dc.contributor.authorCaliebe, Almuth
dc.contributor.authorChrzanowska, Krystyna
dc.contributor.authorCogulu, Ozgur
dc.contributor.authorCristofoli, Francesca
dc.contributor.authorCzeschik, Johanna Christina
dc.contributor.authorDevriendt, Koenraad
dc.contributor.authorDotti, Maria Teresa
dc.contributor.authorElcioglu, Nursel
dc.contributor.authorGener, Blanca
dc.contributor.authorGoecke, Timm O.
dc.contributor.authorKrajewska-Walasek, Malgorzata
dc.contributor.authorGuillen-Navarro, Encarnacion
dc.contributor.authorHayek, Joussef
dc.contributor.authorHouge, Gunnar
dc.contributor.authorKilic, Esra
dc.contributor.authorSimsek-Kiper, Pelin Ozlem
dc.contributor.authorLopez-Gonzalez, Vanesa
dc.contributor.authorKuechler, Alma
dc.contributor.authorLyonnet, Stanislas
dc.contributor.authorMari, Francesca
dc.contributor.authorMarozza, Annabella
dc.contributor.authorDramard, Michele Mathieu
dc.contributor.authorMikat, Barbara
dc.contributor.authorMorin, Gilles
dc.contributor.authorMorice-Picard, Fanny
dc.contributor.authorOzkinay, Ferda
dc.contributor.authorRauch, Anita
dc.contributor.authorRenieri, Alessandra
dc.contributor.authorTinschert, Sigrid
dc.contributor.authorUtine, G. Eda
dc.contributor.authorVilain, Catheline
dc.contributor.authorVivarelli, Rossella
dc.contributor.authorZweier, Christiane
dc.contributor.authorNuernberg, Peter
dc.contributor.authorRahmann, Sven
dc.contributor.authorVermeesch, Joris
dc.contributor.authorLuedecke, Hermann-Josef
dc.contributor.authorZeschnigk, Michael
dc.contributor.authorWollnik, Bernd
dc.date.accessioned2023-02-21T12:42:47Z
dc.date.available2023-02-21T12:42:47Z
dc.date.issued2013-01-01
dc.description.abstractChromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. Denovodominant 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.
dc.description.issue25
dc.description.issueDEC 20
dc.description.pages5121-5135
dc.description.volume22
dc.identifier.doi10.1093/hmg/ddt366
dc.identifier.urihttps://hdl.handle.net/11443/2847
dc.identifier.urihttp://dx.doi.org/10.1093/hmg/ddt366
dc.identifier.wosWOS:000327800400004
dc.publisherOXFORD UNIV PRESS
dc.relation.ispartofHUMAN MOLECULAR GENETICS
dc.titleA comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling
dc.typeArticle

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