Stessman, H.A., Xiong, B., Coe, B.P., Wang, T., Hoekzema, K., Fenckova, M., Kvarnung, M., Gerdts, J., Trinh, S., Cosemans, N., Vives, L., Lin, J., Turner, T.N., Santen, G., Ruivenkamp, C., Kriek, M., van Haeringen, A., Aten, E., Friend, K., Liebelt, J., Barnett, C., Haan, E., Shaw, M., Gecz, J., Anderlid, B.M., Nordgren, A., Lindstrand, A., Schwartz, C., Kooy, R.F., Vandeweyer, G., Helsmoortel, C., Romano, C., Alberti, A., Vinci, M., Avola, E., Giusto, S., Courchesne, E., Pramparo, T., Pierce, K., Nalabolu, S., Amaral, D.G., Scheffer, I.E., Delatycki, M.B., Lockhart, P.J., Hormozdiari, F., Harich, B., Castells-Nobau, A., Xia, K., Peeters, H., Nordenskjöld, M., Schenck, A., Bernier, R.A., Eichler, E.E. (2017). Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.  Nat. Genet. 49(4): 515--526.

FBrf0235148

Research paper

Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most of the related pathogenic genes are not known. We sequenced 208 candidate genes from >11,730 cases and >2,867 controls. We identified 91 genes, including 38 new NDD genes, with an excess of de novo mutations or private disruptive mutations in 5.7% of cases. Drosophila functional assays revealed a subset with increased involvement in NDDs. We identified 25 genes showing a bias for autism versus intellectual disability and highlighted a network associated with high-functioning autism (full-scale IQ >100). Clinical follow-up for NAA15, KMT5B, and ASH1L highlighted new syndromic and nonsyndromic forms of disease.

PMC5374041 (PMC) (EuropePMC)