THE FRIEDREICH ATAXIA GENE ENCODES A NOVEL PHOSPHATIDYLINOSITOL-4-PHOSPHATE 5-KINASE

The STM7 gene on chromosome 9 was recently 'excluded' as a candidate f or Friedreich's ataxia following the identification of an expanded int ronic GAA triplet repeat in the adjacent gene, X25, in patients with t he disease. Using RT-PCR, northern and sequence analyses, we now demon strate that X25 comprises part of the STM7 gene, contributing to at le ast four splice variants, and report the identification of new coding sequences. Functional analysis of the STM7 recombinant protein corresp onding to the reported 2.7-kilobase transcript has demonstrated PtdIns P 5-kinase activity, supporting the idea that the disease is caused by a defect in the phosphoinositide pathway, possibly affecting vesicula r trafficking or synaptic transmission.