To identify responsible genes and survey the custom-made therapy for West syndrome

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Background : ARX is a homeobox gene on Xp22.13 and is crucial to the development of interneurons in the fetal brain. Null mutation of ARX causes anomalies of the brain and the external genitalia, while missense or polyalanine expansion mutation causes nonsyndromic or syndromic mental retardation including West syndrome. In this study, we did ARX mutation screening in patients with West syndrome and analyzed the genotype-phenotype correlation associated with ARX mutation.Methods : Blood samples were collected from 29 patients (21 males) with cryptogenic or idiopathic West syndrome with the informed consent. Genomic DNA was extracted and five exons and flanking introns of ARX gene were amplified with PCR. Direct sequencing was performed on the product with expanded size after the electrophoresis and the product showing a heteroduplex pattern on the DHPLC mutation screening.Results : A mutation, 333_334ins(GCG)_7, was found in a boy, which is supposed to expand the first polyalanine tract from 16 to 23 alanine residues. His mother was a heterozygous carrier and his young brother had the same mutation and showed tonic seizures and dystonia from infancy.Conclusions : The same mutation has been already reported in 12 patients from 3 families. All patients including our cases show epileptic attacks in infancy, profound mental retardation, and inability to walk. West syndrome is found in eight of 11 patients and myoclonic seizure in 11 of 13 patients. They are more frequent than those in patients with the second polyalanine expansion. The first polyalanine expansion is associated with more severe and specific phenotype than the second polyalanine expansion.