Journal article
Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability
B Cogné, S Ehresmann, E Beauregard-Lacroix, J Rousseau, T Besnard, T Garcia, S Petrovski, S Avni, K McWalter, PR Blackburn, SJ Sanders, K Uguen, J Harris, JS Cohen, M Blyth, A Lehman, J Berg, MH Li, U Kini, S Joss Show all
American Journal of Human Genetics | CELL PRESS | Published : 2019
Abstract
Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first ..
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Awarded by National Institute of Child Health and Human Development
Funding Acknowledgements
We would like to thank all families for participating in this study. This work was supported in part by grants from: the French Ministry of Health and the Health Regional Agency from Poitou-Charentes (HUGODIMS, 2013, RC14_0107) to S.B.; the National Institute of Neurological Disorders and Stroke (The Epilepsy Phenome/Genome Project NS053998; Epi4K NS077364, NS077274, NS077303, and NS077276) to D.L. and D.B.G.; the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grant (HD064667) to D.A.S.; NINDS R35 NS105078 to J.R.L.; the National Human Genome Research Institute (NHGRI) and National Heart, Lung, and Blood Institute (NHLBI) to the Baylor-Hopkins Center for Mendelian Genomics (UM1 HG006542); NHGRI K08 HG008986 to J.E.P.; the Duke Genome Sequencing Clinic to V.S. and J.S.; the intramural research program of the NHGRI (grant HG200328 12) to L.G.B., J. J. J., and J.C.S.; the US National Institute of Mental Health grant R01MH101221 to E.E.E.; the Kids Brain Health Network and Dart NeuroScience to F.B.; and Mining for Miracles, British Columbia Children's Hospital Foundation, and Genome British Columbia to the CAUSES Study. We thank the Canadian Institutes of Health Research (CIHR) and Fonds de la recherche en sante du Quebec (FRSQ) for clinician-scientist awards to P.M.C.; and the Mayo Clinic Center for Individualized Medicine (CIM) for supporting this research through the CIM Investigative and Functional Genomics Program. We are grateful to the members of the Canadian Center for Computational Genomics and the McGill University and Genome Quebec Innovation Center for their help in bioinformatics analysis.