Mental retardation (MR) involves a complex collection of clinically and genetically diverse disorders. Diagnosis of MR is typically based on three main criteria: onset of symptoms before the age of 18, intellectual abilities significantly lower than average, and reduced adaptive skills. Individuals with MR tend to struggle in areas including communication, health, interpersonal/social skills, leisure, safety, self-guidance and care, school performance, and work.                     

X-linked mental retardation (XLMR) is associated with more than 200 conditions linked to >90 genes on the X chromosome. XLMR affects approximately 1/600-1/1000 males, as well as a significant number of females.   Mutations in these genes have been shown to be an underlying cause of mental retardation, which may or may not be associated with other congenital anomalies, developmental delay, autism, dysmorphism, and numerous genetic syndromes.  One of the XLMR associated genes is ATRX.

The ATRX gene, located at Xq21.1, contains 35 exons and encodes the ATRX protein.   In vitro studies suggest the ATRX protein is involved in chromatin remodeling and regulation of gene expression. Mutations of various types in ATRX have been shown to be associated with alpha-thalassemia X-linked mental retardation (ATRX) syndrome, which is generally characterized by severe to profound mental retardation, distinctive craniofacial features, genital anomalies, and alpha-thalassemia (Gibbons R. Orphanet J Rare Dis. 2006;1:15).