Journal article

Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID

BWM Van Bon, BP Coe, R Bernier, C Green, J Gerdts, K Witherspoon, T Kleefstra, MH Willemsen, R Kumar, P Bosco, M Fichera, D Li, D Amaral, F Cristofoli, H Peeters, E Haan, C Romano, HC Mefford, I Scheffer, J Gecz Show all

Molecular Psychiatry | Published : 2016

Abstract

Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) maps to the Down syndrome critical region; copy number increase of this gene is thought to have a major role in the neurocognitive deficits associated with Trisomy 21. Truncation of DYRK1A in patients with developmental delay (DD) and autism spectrum disorder (ASD) suggests a different pathology associated with loss-of-function mutations. To understand the phenotypic spectrum associated with DYRK1A mutations, we resequenced the gene in 7162 ASD/DD patients (2446 previously reported) and 2169 unaffected siblings and performed a detailed phenotypic assessment on nine patients. Comparison of our data and published cases..

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University of Melbourne Researchers

Grants

Awarded by National Institutes of Health


Funding Acknowledgements

We thank the patients and their parents for participation. We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A Beaudet, R Bernier, J Constantino, E Cook, E Fombonne, D Geschwind, R Goin-Kochel, E Hanson, D Grice, A Klin, D Ledbetter, C Lord, C Martin, D Martin, R Maxim, J Miles, O Ousley, K Pelphrey, B Peterson, J Piggot, C Saulnier, M State, W Stone, J Sutcliffe, C Walsh, Z Warren, E Wijsman). We appreciate obtaining access to phenotypic data on the Simons Foundation Autism Research Initiative (SFARI) Base. Approved researchers can obtain the SSC population dataset described in this study (https://ordering.base.sfari.org/similar to browse_collection/archive[ssc_v13]/ui: view) by applying at https://base.sfari.org. This study was financially supported by (1) the Ter Meulen Fonds (stipendium to BvB), (2) the Dutch Organisation for Health Research and Development: ZON-MW grants 917-86-319 (BBAdV) and 912-12-109 (BBAdV), and (3) the Simons Foundation Autism Research Initiative (SFARI 303241) and National Institutes of Health (NIH) grant R01MH101221 to EEE. EEE is an Investigator of the Howard Hughes Medical Institute. FC is a PhD aspirant of the Research Foundation Flanders (FWO).