Mutation screening of the Aristaless-related homeobox (ARX) gene in Thai pediatric patients with delayed development: first report from Thailand

Abstract

Mutations in the Aristaless-related homeobox gene, ARX, have been a cause of X-linked mental retardation (XLMR) and are responsible for a vast phenotypic spectrum including syndromic and non-syndromic forms of mental retardation. Since the gene was initially identified, it has been generally screened in several patients with XLMR. This study is the first report of ARX mutational screening in Thai pediatric patients with delayed development. Two hundred and fifty-one patients participated in this study. Two hundred and three of the 251 patients were initially referred for molecular diagnosis of the Fragile XA syndrome and had negative test results. The remaining 48 patients were specifically recruited for the ARX mutational analysis and had previously reported phenotypes of the ARX mutations. Screening for the c.428_451 dup mutation was performed in all samples. Screening for other point mutations in all coding exons was performed in all 48 patients recruited for the ARX mutational analysis and in 29 patients initially referred for diagnosis of the Fragile XA syndrome who had two or more affected males in the family suggesting an X-linked inheritance pattern. Two patients were found to have the c.428_451 dup mutation. Considering genotype-phenotype correlation, we suggest screening of the most common mutation, the c.428_451 dup mutation by PCR, in patients with infantile spasm syndrome, Partington syndrome and non-syndromic X-linked mental retardation. Screening in patients who have negative Fragile XA test results should be considered when no other known causes of mental retardation are identified especially in families with suggestive X-linked inheritance pattern.