Fig. 1
From: AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders
GRIA2 intragenic de-novo variants identified in this study. a Schematic of the human GluA2 protein (NP_000817.2) indicating the positions of twelve missense changes (dot arrows), two frameshift deletions (cross arrows), two splice-site variants (arrows) and an in-frame deletion (dot arrow). Glutamate binding regions are displayed in red, flip/flop alternatively spliced region is represented in green. b Left panel: Patient 1, carrying the de-novo p.W788L GluA2Flop variant, at 3 years, exhibitinghypotonia and an oculogyric crisis; he is wheelchair dependent. Middle left panel: Patient 2 (top) carrying the de-novo p.P528_K530del in-frame deletion, at 12 years; Patient 3 (bottom) carrying the de-novo p.D611N variant, at 18 years, exhibiting hand-wringing suggestive of RTT. Middle right panel: Patient 7, carrying the de-novo p.Q607E/p.R607G heterozygous mutation (affecting the Q/R editing site) at 10 years, exhibiting hand-wringing as part of a RTT-like presentation. Right panel: Patient 10 (top) carrying the de-novo p.F595LfsX37 variant, at 5 years; Patient 12 (bottom) carrying the de-novo p.P286LfsX14 at 6 years. c Multiple alignment showing GluA2 protein complete conservation across species and inter AMPAR homolog subunits (GluA1, GluA3, and GluA4) alignment. Human GRIA2 (NP_000817.2), mouse GRIA2 (NP_001077275.1), bos taurus GRIA2 (NP_001069789.2), gallus gallus GRIA2 (NP_001001775.2), danio rerio (NP_571970.2), drosophila melanogaster (NP_476855.1), Human GRIA1 (NP_000818.2) Human GRIA3 (NP_015564.4), and Human GRIA4 (NP_000820.3)
