Person: YEŞİL, GÖZDE
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Publication Metadata only Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes(2015-02-01T00:00:00Z) Yuan, Bo; Pehlivan, Davut; Karaca, Ender; Patel, Nisha; Charng, Wu-Lin; Gambin, Tomasz; Gonzaga-Jauregui, Claudia; Sutton, V. Reid; Yesil, Gozde; Bozdogan, Sevcan Tug; Tos, Tulay; Koparir, Asuman; Koparir, Erkan; Beck, Christine R.; Gu, Shen; Aslan, Huseyin; Yuregir, Ozge Ozalp; Al Rubeaan, Ha Lid; Alnaqeb, Dhekra; Alshammari, Muneera J.; Bayram, Yavuz; Atik, Mehmed M.; Aydin, Hatip; Geckinli, B. Bilge; Seven, Mehmet; Ulucan, Hakan; Fenercioglu, Elif; Ozen, Mustafa; Jhangiani, Shalini; Muzny, Donna M.; Boerwinkle, Eric; Tuysuz, Beyhan; Alkuraya, Fowzan S.; Gibbs, Richard A.; Lupski, James R.; YEŞİL, GÖZDECornelia 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.