Background: Mutations in the human aristaless-related homeobox (ARX) gene are amongst the major causes of developmental and neurological disorders. They are responsible for a wide spectrum of phenotypes, including nonsyndromic X-linked intellectual disability (NS-XLID), and syndromic (XLIDS) forms such as X-linked lissencephaly with abnormal genitalia (XLAG), Partington syndrome (PRTS), and X-linked infantile spasm syndrome (ISSX). The recurrent 24 bp duplication mutation, c.428_451dup(24 bp), is the most frequent ARX mutation, which accounts for ~40% of all cases reported to date.
Methods: We have screened the entire coding sequences of the ARX gene in 65 Iranian families with intellectual disabilities in order to obtain the relative prevalence of ARX mutations. At first these families were screened for the most recurrent mutation, the c.428_451dup(24 bp). For samples with negative results, single strand conformation polymorphism (SSCP) analysis was performed.
Results: We identified one family with the c.428_451dup(24 bp) duplication. Three shifts (one shift in exon 5 and two shifts in exon 4) were also identified among the total families. According to the results of the sequencing analysis, two shifts were not associated with any mutation and the other one was a c.1347C>T (p.G449G) substitution in exon 4.
Conclusion: Hence, we suggest that molecular analysis of ARX mutations as a second cause of XLID should be considered as routine diagnostic procedure in any male who presents with either NS-XLID or XLIDS.