Subtle functional defects in the Arf-specific guanine nucleotide exchange factor IQSEC2 cause non-syndromic X-linked intellectual disability

C Shoubridge; R S Walikonis; J Gécz; Robert J Harvey

doi:10.4161/sgtp.1.2.13285

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Subtle functional defects in the Arf-specific guanine nucleotide exchange factor IQSEC2 cause non-syndromic X-linked intellectual disability

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Subtle functional defects in the Arf-specific guanine nucleotide exchange factor IQSEC2 cause non-syndromic X-linked intellectual disability

C Shoubridge, R S Walikonis, J Gécz and Robert J Harvey

Small GTPases, Vol.1(2), pp.98-103

2010

DOI: https://doi.org/10.4161/sgtp.1.2.13285

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Abstract

Arf GTPases

BRAG1

IQSEC2

genetics

IQ-ArfGEF

Mutations in IQSEC2, a guanine nucleotide exchange factor for the ADP-ribosylation factor (Arf) family of small GTPases have recently been shown to cause non-syndromic X-linked intellectual disability (ID), characterised by substantial limitations in intellectual functioning and adaptive behaviour. This discovery was revealed by a combination of large-scale resequencing of the X chromosome, and key functional assays that revealed a reduction, but not elimination, of IQSEC2 GEF activity for mutations affecting conserved amino acids in the IQ-like and Sec7 domains. Compromised GTP binding activity of IQSEC2 leading to reduced activation of selected Arf substrates (Arf1, Arf6) is expected to impact on cytoskeletal organization, dendritic spine morphology and synaptic organisation. This study highlights the need for further investigation of the IQSEC gene family and Arf GTPases in neuronal morphology and synaptic function, and suggests that the genes encoding the ArfGEFs IQSEC1 and IQSEC3 should be considered as candidates for screening in autosomal ID. © 2010 Landes Bioscience.

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Title: Subtle functional defects in the Arf-specific guanine nucleotide exchange factor IQSEC2 cause non-syndromic X-linked intellectual disability
Authors: C Shoubridge (Author) - University of Adelaide
R S Walikonis (Author) - University of Connecticut, United States
J Gécz (Author) - University of Adelaide
Robert J Harvey (Author) - University College London, United Kingdom
Publication details: Small GTPases, Vol.1(2), pp.98-103
Publisher: Taylor & Francis Inc.
Date published: 2010
DOI: 10.4161/sgtp.1.2.13285
ISSN: 2154-1248
Copyright note: Copyright © 2010 Landes Bioscience. This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99451275202621
Output Type: Journal article

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