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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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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