Wieczorek, Dagmar ORCID: 0000-0003-2812-6492, Boegershausen, Nina, Beleggia, Filippo ORCID: 0000-0003-0234-7094, Steiner-Haldenstaett, Sabine, Pohl, Esther, Li, Yun, Milz, Esther, Martin, Marcel ORCID: 0000-0002-0680-200X, Thiele, Holger, Altmueller, Janine, Alanay, Yasemin ORCID: 0000-0003-0683-9731, Kayserili, Hulya ORCID: 0000-0003-0376-499X, Klein-Hitpass, Ludger, Bohringer, Stefan, Wollstein, Andreas, Albrecht, Beate, Boduroglu, Koray ORCID: 0000-0001-6260-1942, Caliebe, Almuth ORCID: 0000-0003-2157-425X, Chrzanowska, Krystyna ORCID: 0000-0003-3888-0624, Cogulu, Ozgur, Cristofoli, Francesca, Czeschik, Johanna Christina ORCID: 0000-0002-9254-0084, Devriendt, Koenraad, Dotti, Maria Teresa, Elcioglu, Nursel, Gener, Blanca, Goecke, Timm O., Krajewska-Walasek, Malgorzata ORCID: 0000-0001-8721-210X, Guillen-Navarro, Encarnacion, Hayek, Joussef, Houge, Gunnar, Kilic, Esra, Simsek-Kiper, Pelin Ozlem, Lopez-Gonzalez, Vanesa, Kuechler, Alma, Lyonnet, Stanislas ORCID: 0000-0001-5426-9417, Mari, Francesca ORCID: 0000-0003-1992-1654, Marozza, Annabella, Dramard, Michele Mathieu, Mikat, Barbara, Morin, Gilles, Morice-Picard, Fanny, Ozkinay, Ferda, Rauch, Anita ORCID: 0000-0003-2930-3163, Renieri, Alessandra ORCID: 0000-0002-0846-9220, Tinschert, Sigrid, Utine, G. Eda, Vilain, Catheline, Vivarelli, Rossella, Zweier, Christiane ORCID: 0000-0001-8002-2020, Nuernberg, Peter, Rahmann, Sven, Vermeesch, Joris, Luedecke, Hermann-Josef, Zeschnigk, Michael and Wollnik, Bernd (2013). A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling. Hum. Mol. Genet., 22 (25). S. 5121 - 5136. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2083

Full text not available from this repository.

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. 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wieczorek, DagmarUNSPECIFIEDorcid.org/0000-0003-2812-6492UNSPECIFIED
Boegershausen, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beleggia, FilippoUNSPECIFIEDorcid.org/0000-0003-0234-7094UNSPECIFIED
Steiner-Haldenstaett, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pohl, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, YunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milz, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, MarcelUNSPECIFIEDorcid.org/0000-0002-0680-200XUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alanay, YaseminUNSPECIFIEDorcid.org/0000-0003-0683-9731UNSPECIFIED
Kayserili, HulyaUNSPECIFIEDorcid.org/0000-0003-0376-499XUNSPECIFIED
Klein-Hitpass, LudgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bohringer, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wollstein, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Albrecht, BeateUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boduroglu, KorayUNSPECIFIEDorcid.org/0000-0001-6260-1942UNSPECIFIED
Caliebe, AlmuthUNSPECIFIEDorcid.org/0000-0003-2157-425XUNSPECIFIED
Chrzanowska, KrystynaUNSPECIFIEDorcid.org/0000-0003-3888-0624UNSPECIFIED
Cogulu, OzgurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cristofoli, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czeschik, Johanna ChristinaUNSPECIFIEDorcid.org/0000-0002-9254-0084UNSPECIFIED
Devriendt, KoenraadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dotti, Maria TeresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elcioglu, NurselUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gener, BlancaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goecke, Timm O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krajewska-Walasek, MalgorzataUNSPECIFIEDorcid.org/0000-0001-8721-210XUNSPECIFIED
Guillen-Navarro, EncarnacionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hayek, JoussefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Houge, GunnarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilic, EsraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simsek-Kiper, Pelin OzlemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez-Gonzalez, VanesaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuechler, AlmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lyonnet, StanislasUNSPECIFIEDorcid.org/0000-0001-5426-9417UNSPECIFIED
Mari, FrancescaUNSPECIFIEDorcid.org/0000-0003-1992-1654UNSPECIFIED
Marozza, AnnabellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dramard, Michele MathieuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mikat, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morin, GillesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morice-Picard, FannyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ozkinay, FerdaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rauch, AnitaUNSPECIFIEDorcid.org/0000-0003-2930-3163UNSPECIFIED
Renieri, AlessandraUNSPECIFIEDorcid.org/0000-0002-0846-9220UNSPECIFIED
Tinschert, SigridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Utine, G. EdaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vilain, CathelineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vivarelli, RossellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zweier, ChristianeUNSPECIFIEDorcid.org/0000-0001-8002-2020UNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rahmann, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vermeesch, JorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luedecke, Hermann-JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeschnigk, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wollnik, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-469960
DOI: 10.1093/hmg/ddt366
Journal or Publication Title: Hum. Mol. Genet.
Volume: 22
Number: 25
Page Range: S. 5121 - 5136
Date: 2013
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2083
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FORSSMAN-LEHMANN-SYNDROME; MENTAL-RETARDATION; MUTATIONS; SWI/SNF; COMPLEX; PHF6; COMPONENTS; ARID1BMultiple languages
Biochemistry & Molecular Biology; Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/46996

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item