1p34.3 deletion involving GRIK3: Further clinical implication of GRIK family glutamate receptors in the pathogenesis of developmental delay. Issue 2 (25th November 2013)

• Record Type: Journal Article
• Authors: Takenouchi, Toshiki; Hashida, Noriko; Torii, Chiharu; Kosaki, Rika; Takahashi, Takao; Kosaki, Kenjiro
• Is Part Of: American journal of medical genetics. Volume 164:Issue 2(2014.)
• Page Start: 456
• Page End: 460
• Publication Date: 2013-11-25
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36240
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajmga36240-sec-0001" sec-type="section"> <p>A growing body of evidence suggests an association between microdeletion/microduplication and schizophrenia/intellectual disability. Abnormal neurogenesis and neurotransmission have been implicated in the pathogenesis of these neuropsychiatric and neurodevelopmental disorders. The kainate/AMPA‐type ionotropic glutamate receptor (GRIK = glutamate receptor, ionotropic, kainate) plays a critical role in synaptic potentiation, which is an essential process for learning and memory. Among the five known GRIK family members, haploinsufficiency of <italic>GRIK1</italic>, <italic>GRIK2</italic>, and <italic>GRIK4</italic> are known to cause developmental delay, whereas the roles of <italic>GRIK3</italic> and <italic>GRIK5</italic> remain unknown. Herein, we report on a girl who presented with a severe developmental delay predominantly affecting her language and fine motor skills. She had a 2.6‐Mb microdeletion in 1p34.3 involving <italic>GRIK3</italic>, which encodes a principal subunit of the kainate‐type ionotropic glutamate receptor. Given its strong expression pattern in the central nervous system and the biological function of GRIK3 in presynaptic neurotransmission, the haploinsufficiency of <italic>GRIK3</italic> is likely to be responsible for the severe developmental delay in the proposita. A review of genetic alterations and the phenotypic effects of all the GRIK family members support this hypothesis. The current observation of a microdeletion involving <italic>GRIK3</italic>, a kainate‐type ionotropic glutamate receptor subunit, and the neurodevelopmental manifestation in the absence of major dysmorphism provides further clinical implication of the possible role of GRIK family glutamate receptors in the pathogenesis of developmental delay. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>