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Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes

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dc.contributor.authorYuan, Bo
dc.contributor.authorPehlivan, Davut
dc.contributor.authorKaraca, Ender
dc.contributor.authorPatel, Nisha
dc.contributor.authorCharng, Wu-Lin
dc.contributor.authorGambin, Tomasz
dc.contributor.authorGonzaga-Jauregui, Claudia
dc.contributor.authorSutton, V. Reid
dc.contributor.authorYesil, Gozde
dc.contributor.authorBozdogan, Sevcan Tug
dc.contributor.authorTos, Tulay
dc.contributor.authorKoparir, Asuman
dc.contributor.authorKoparir, Erkan
dc.contributor.authorBeck, Christine R.
dc.contributor.authorGu, Shen
dc.contributor.authorAslan, Huseyin
dc.contributor.authorYuregir, Ozge Ozalp
dc.contributor.authorAl Rubeaan, Ha Lid
dc.contributor.authorAlnaqeb, Dhekra
dc.contributor.authorAlshammari, Muneera J.
dc.contributor.authorBayram, Yavuz
dc.contributor.authorAtik, Mehmed M.
dc.contributor.authorAydin, Hatip
dc.contributor.authorGeckinli, B. Bilge
dc.contributor.authorSeven, Mehmet
dc.contributor.authorUlucan, Hakan
dc.contributor.authorFenercioglu, Elif
dc.contributor.authorOzen, Mustafa
dc.contributor.authorJhangiani, Shalini
dc.contributor.authorMuzny, Donna M.
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorTuysuz, Beyhan
dc.contributor.authorAlkuraya, Fowzan S.
dc.contributor.authorGibbs, Richard A.
dc.contributor.authorLupski, James R.
dc.contributor.institutionauthorYEŞİL, GÖZDE
dc.date.accessioned2020-10-29T22:26:53Z
dc.date.available2020-10-29T22:26:53Z
dc.date.issued2015-02-01T00:00:00Z
dc.description.abstractCornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder that presents with extensive phenotypic variability, including facial dysmorphism, developmental delay/intellectual disability (DD/ID), abnormal extremities, and hirsutism. About 65% of patients harbor mutations in genes that encode subunits or regulators of the cohesin complex, including NIPBL, SMC1A, SMC3, RAD21, and HDAC8. Wiedemann-Steiner syndrome (WDSTS), which shares CdLS phenotypic features, is caused by mutations in lysine-specific methyltransferase 2A (KMT2A). Here, we performed whole-exome sequencing (WES) of 2 male siblings clinically diagnosed with WDSTS; this revealed a hemizygous, missense mutation in SMC1A that was predicted to be deleterious. Extensive clinical evaluation and WES of 32 Turkish patients clinically diagnosed with CdLS revealed the presence of a de novo heterozygous nonsense KMT2A mutation in 1 patient without characteristic WDSTS features. We also identified de nova heterozygous mutations in SMC3 or SMC1A that affected RNA splicing in 2 independent patients with combined CdLS and WDSTS features. Furthermore, in families from 2 separate world populations segregating an autosomal-recessive disorder with CdLS-like features, we identified homozygous mutations in TAF6, which encodes a core transcriptional regulatory pathway component. Together, our data, along with recent transcriptome studies, suggest that CdLS and related phenotypes may be -transcriptomopathies- rather than cohesinopathies.
dc.identifier.citationYuan B., Pehlivan D., Karaca E., Patel N., Charng W., Gambin T., Gonzaga-Jauregui C., Sutton V. R. , Yesil G., Bozdogan S. T. , et al., -Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes-, JOURNAL OF CLINICAL INVESTIGATION, cilt.125, ss.636-651, 2015
dc.identifier.doi10.1172/jci77435
dc.identifier.scopus84961290013
dc.identifier.urihttp://hdl.handle.net/20.500.12645/26622
dc.identifier.wosWOS:000348962700021
dc.titleGlobal transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes
dc.typeArticle
dspace.entity.typePublication
local.avesis.idb2a69659-eb03-4121-bd33-48c5e7e5c5cf
local.publication.isinternational1
relation.isAuthorOfPublicationb653abbc-327a-4b3b-a227-f3344d8d6b70
relation.isAuthorOfPublication.latestForDiscoveryb653abbc-327a-4b3b-a227-f3344d8d6b70
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