Journal article

Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders

Jacob R Stolz, Kendall M Foote, Hermine E Veenstra-Knol, Rolph Pfundt, Sanne W ten Broeke, Nicole de Leeuw, Laura Roht, Sander Pajusalu, Reelika Part, Ionella Rebane, Katrin Ounap, Zornitza Stark, Edwin P Kirk, John A Lawson, Sebastian Lunke, John Christodoulou, Raymond J Louie, R Curtis Rogers, Jessica M Davis, A Micheil Innes Show all

AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 2021

Abstract

Kainate receptors (KARs) are glutamate-gated cation channels with diverse roles in the central nervous system. Bi-allelic loss of function of the KAR-encoding gene GRIK2 causes a nonsyndromic neurodevelopmental disorder (NDD) with intellectual disability and developmental delay as core features. The extent to which mono-allelic variants in GRIK2 also underlie NDDs is less understood because only a single individual has been reported previously. Here, we describe an additional eleven individuals with heterozygous de novo variants in GRIK2 causative for neurodevelopmental deficits that include intellectual disability. Five children harbored recurrent de novo variants (three encoding p.Thr660Ly..

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Grants

Awarded by National Institute for Neurological Disorders and Stroke


Awarded by National Health and Medical Research Council


Awarded by Estonian Research Council


Funding Acknowledgements

This work was supported by grants from the National Institute for Neurological Disorders and Stroke to G.T.S. (R01NS105502) and to G.L.C. (R00NS089858). G.T.S. thanks the Murphy family for additional support for these studies. The Acute Care Flagship of the Australian Genomics Health Alliances is supported by grants from the Sydney Children's Hospital Network and the National Health and Medical Research Council (GNT1113531). K.O~. and S.P. were supported by Estonian Research Council grants PRG471, MOBTP175, and PUTJD827. The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. We are grateful to the families of the individuals for their willingness to participate in this effort.