Koolen, D.A., Kramer, J.M., Neveling, K., Nillesen, W.M., Moore-Barton, H.L., Elmslie, F.V., Toutain, A., Amiel, J., Malan, V., Tsai, A.C., Cheung, S.W., Gilissen, C., Verwiel, E.T., Martens, S., Feuth, T., Bongers, E.M., de Vries, P., Scheffer, H., Vissers, L.E., de Brouwer, A.P., Brunner, H.G., Veltman, J.A., Schenck, A., Yntema, H.G., de Vries, B.B. (2012). Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome.  Nat. Genet. 44(6): 639--641.

FBrf0218489

Research paper

We show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation. RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes.