NOVEL MUTATION IN THE ARX GENE IN TWO SIBLINGS WITH MENTAL RETARDATION, EPILEPSY AND DYSTONIA

Objectives: ARX is a homeobox transcription factor, which is expressed in early embryonic brain. ARX mutations result in a spectrum of phenotype including X-linked West syndrome, lissencephaly with abnormal genitalia and Partington syndrome with obvious genotype-phenotype correlation. Here, we identified a novel mutation in two siblings with mental retardation, epilepsy and dystonia.

Methods: Genomic DNA from peripheral blood of the patients were extracted. Each exon of ARX gene was amplified by PCR, followed by direct sequencing.

Results: Two siblings were delivered of unconsanguineous parents. The elder brother, aged eleven years, severely delayed in developmental milestones after birth. He was diagnosed with West syndrome at two months of age. He had undescended testis. Additionally, he was noted severe truncal dystonia at eight years of age. His younger brother, aged seven years, had a similar disorder, but his epilepsy did not fulfill the criteria of West syndrome, and his external genetalia was normal. EEG of both cases showed very frequent spikes on the frontal area. Brain MRI revealed diffuse brain atrophy, but no obvious cortical dysplasia or Lissencephaly was detected. Mutation analysis showed a complex alteration with 4 nucleotide substitutions in exon 1 of ARX gene, which leads to C16X in both cases.

Conclusion: We identified a family with mental retardation, epilepsy and dystonia with an early truncation in ARX. Despite the fact that the majority of patients with ARX truncating mutations represent severe brain malformation, our cases had no such findings. Suggesting the C16X mutation may not result in a complete loss-of-function.