STK25 is a candidate gene for pseudopseudohypoparathyroidism

We determined the chromosomal location of the mouse gene Stk25, encoding a member of the Ste20/PAK family of serine/threonine kinases, by interspecifi c backcross analysis. We mapped Stk25 to the central region of mouse chromo some 1 linked to Chrng (formerly Acrg) and En1. This central region of mous e chromosome 1 shares a region of homology with the long arm of human chrom osome 2, suggesting that the human homologue of Stk25 would also map to 2q. We proved this prediction of syntenic homology correct by mapping human ST K25 to 2q37. Deletion of the 2q37 region has been implicated in the express ion of pseudopseudohypoparathyroidism (PPHP), a disease which shares featur es of the Albright hereditary osteodystrophy (AHO) phenotype. To investigat e a pathogenetic relationship between STK25 and PPHP, we carried out fluore scence in situ hybridization (FISH) using an STK25 gene probe and chromosom es from PPHP patients characterized as having small deletions near the dist al end of 2q. PPHP patient DNA showed no hybridization to STK25 genomic DNA , indicating that STK25 is contained within the deleted.,, in conjunction w ith chromosomal region. This finding previous studies demonstrating the rol e of Ste20/PAK kinases in heterotrimeric G protein signaling, suggests that STK25 is a positional candidate gene for PPHP.