Review Article
ARX: A Small Gene with a Crucial Role in X-Linked Intellectual Disability
Shirin Ghadami* and Yeganeh Eshaghkhani
Corresponding Author: Shirin Ghadami, Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Mollasadra Ave, Vanak Square, Tehran, Iran
Received: June 24, 2019; Accepted: July 03, 2019;
Citation: Ghadami S & Eshaghkhani Y. (2019) ARX: A Small Gene with a Crucial Role in X-Linked Intellectual Disability. J Genet Cell Biol, 3(1): 135-139.
Copyrights: ©2019 Ghadami S & Eshaghkhani Y. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 

Intellectual disability is the most common neurodevelopmental defect in the world. This disorder affects 1-3% of the general population. X-linked intellectual disability (XLID) is the frequent form of intellectual disability which includes a heterogeneous group of inherited disorders emerging as various degrees of intellectual disabilities. Phenotypically, XLID is subdivided into syndromic (S-XLID) and non-syndromic (NS-XLID) forms; where two-thirds of the XLID cases are thought to be non-syndromic. Among the non-syndromic form, the aristaless-related homeobox gene (ARX) is one of the ideal candidates to be evaluated in NS-XLID, since its mutations are responsible for about 9.5% of XLID cases. Based on the previous literature, mutations in the ARX gene influence the critical processes associated with brain development. Our bioinformatics results showed that the ARX is a highly conserved protein with a substantial role in an important developmental pathway; and its deficiency can cause irreversible defects, mainly in the brain, that leads to the development of XLID. Moreover, we addressed the structural properties of the ARX protein to decipher the important role of the ARX gene in the integrity of normal brain development.

 

Keywords: ARX, X-linked intellectual disability, Protein structure, Wnt/β-catenin signaling

 

INTRODUCTION

Intellectual disability (ID) is the most frequent neurodevelopmental disorder in the world characterized by an intelligence quotient (IQ) below 70 [1]. The prevalence of ID is approximately 2-3% in the general population [2-8]. ID or associated phenotypes resulted from a monogenic defect are subdivided into 4 categories according to the mode of inheritance, autosomal dominant ID, autosomal recessive ID, X-linked ID and mitochondrial ID [9-13]. Mutations in X-linked genes account for 5-10% of all types of ID and are the most likely causes of ID in males [14].

ARX GENE: STRUCTURE AND FUNCTION

The Aristaless-related homeobox gene (ARX) is located on the Xp22.13. It consists of 5 exons (Figure 1) and is transcribed into 2.8 kb mRNA. The structure of the ARX protein consists of several different compartments, including [15-18]: 1) A highly conserved homeobox domain (repressor domain) that spans the amino acids from 328 to 387