Journal article
De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome
JH Kim, DN Shinde, MRF Reijnders, NS Hauser, RL Belmonte, GR Wilson, DGM Bosch, PA Bubulya, V Shashi, S Petrovski, JK Stone, EY Park, JA Veltman, M Sinnema, CTRM Stumpel, JM Draaisma, J Nicolai, HG Yntema, K Lindstrom, BBA de Vries Show all
American Journal of Human Genetics | Published : 2016
Abstract
The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish..
View full abstractGrants
Awarded by ODAS Stichting
Funding Acknowledgements
We are deeply grateful to all individuals and their families for participating in this study. We thank Dr. Michael Markey (Wright State University) for transcript splicing analysis, Dr. David Goldstein, Jennifer Sullivan, and Nicole Walley (Duke University) for their help in collecting clinical information, Petra de Vries (Radboudumc) and Hermann-Josef Ludecke (University Duisburg-Essen) for technical support, and Dr. Christian Gilissen (Radboudumc) for bioinformatic support. We thank the University of Washington Center for Mendelian Genomics (funded by the National Human Genome Research Institute and National Heart, Lung, and Blood Institute grant 1U54HG006493 to Drs. Debbie Nickerson, Jay Shendure, and Michael Bamshad) and the Radboudumc Genomics Technology Center for family-based sequencing. This work was supported by NIH grants (CA190688 and CA185818 to E.-Y.E.A. and GM084407 to P.A.B.), a start-up fund from the University of South Alabama Mitchell Cancer Institute (to E.-Y.E.A.), the Ohio Board of Regents (to P.A.B.), a California State University Chico Internal Research Grant (to D.L.S.), grants from Stichting ODAS and Vereniging Bartimeus-Sonneheerdt (5781251 to B.B.A.d.V. and D.G.M.B.), and a grant from the Dutch Organization for Health Research and Development (912-12-109 to B.B.A.d.V. and J.A.V.). This study used data generated by the DECIPHER Consortium. A full list of centers who contributed to the generation of the data is available at http://decipher.sanger.ac.uk and via email at decipher@sanger.ac.uk. Funding for the DECIPHER project was provided by the Wellcome Trust.