Abstract
The chromosome 17q21.31 deletion syndrome is a genomic disorder characterized by highly distinctive facial features, moderate-to-severe intellectual disability, hypotonia and friendly behavior. Here, we show that de novo loss-of-function mutations in KANSL1 (also called KIAA1267) cause a full del(17q21.31) phenotype in two unrelated individuals that lack deletion at 17q21.31. These findings indicate that 17q21.31 deletion syndrome is a monogenic disorder caused by haploinsufficiency of KANSL1.
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References
Koolen, D.A. et al. Nat. Genet. 38, 999–1001 (2006).
Sharp, A.J. et al. Nat. Genet. 38, 1038–1042 (2006).
Shaw-Smith, C. et al. Nat. Genet. 38, 1032–1037 (2006).
Koolen, D.A. et al. J. Med. Genet. 45, 710–720 (2008).
Tan, T.Y. et al. J. Med. Genet. 46, 480–489 (2009).
Sharkey, F.H. et al. Cytogenet. Genome Res. 127, 61–66 (2009).
Dubourg, C. et al. Eur. J. Med. Genet. 54, 144–151 (2011).
Cooper, G.M. et al. Nat. Genet. 43, 838–846 (2011).
Wang, K., Li, M. & Hakonarson, H. Nucleic Acids Res. 38, e164 (2010).
Smith, E.R. et al. Mol. Cell Biol. 25, 9175–9188 (2005).
Mendjan, S. et al. Mol. Cell 21, 811–823 (2006).
Cai, Y. et al. J. Biol. Chem. 285, 4268–4272 (2010).
Li, X., Wu, L., Corsa, C.A., Kunkel, S. & Dou, Y. Mol. Cell 36, 290–301 (2009).
Slager, R.E., Newton, T.L., Vlangos, C.N., Finucane, B. & Elsea, S.H. Nat. Genet. 33, 466–468 (2003).
Wilson, H.L. et al. J. Med. Genet. 40, 575–584 (2003).
Acknowledgements
The authors gratefully acknowledge the collaboration of the study participants and their families. This work was supported by a MIUR-University Grant 2011 (to M.Z.). We obtained written informed consent from parents and approval from the Ethics Committee of our institution for this study.
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M.Z. designed the study and drafted the manuscript. D.O. and S.L. performed a-CGH. M.M. performed FISH analysis. E.M., C.S. and D.B. referred patients. P.C. conducted the bioinformatic analysis. G.N. critically reviewed the manuscript. G.M. performed sequencing analysis and validation.
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Supplementary Table 1, Supplementary Methods, Supplementary Note and Supplementary Figures 1–5 (PDF 562 kb)
Supplementary Table 2
Gene Ontology (XLS 224 kb)
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Zollino, M., Orteschi, D., Murdolo, M. et al. Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotype. Nat Genet 44, 636–638 (2012). https://doi.org/10.1038/ng.2257
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DOI: https://doi.org/10.1038/ng.2257
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