PHOG, A CANDIDATE GENE FOR INVOLVEMENT IN THE SHORT STATURE OF TURNER-SYNDROME

The abnormalities seen in Turner syndrome (monosomy X) presumably resu lt from haploinsufficiency of certain genes on the X chromosome, Gene dosage considerations lead to the prediction that the culpable genes e scape X inactivation and have functional homologs on the Y chromosome, Among the genes with these characteristics are those residing in the pseudoautosomal regions (PAR) of the sex chromosomes, A pseudoautosoma l location for a dosage-sensitive locus involved in stature has been s uggested based on the analyses of patients with deletions of a specifi c segment of the short arm PAR; hemizygosity for this putative locus p robably also contributes to the short stature in Turner individuals, W e have isolated a gene from the critical deleted region that encodes a novel homeodomain-containing transcription factor and is expressed at highest levels in osteogenic cells, We have named the gene PHOG, for pseudoautosomal homeobox-containing osteogenic gene, Its deletion in p atients with short stature, the predicted altered dosage in 45,X indiv iduals, along with the nature of the encoded protein and its expressio n pattern, make PHOG an attractive candidate for involvement in the sh ort stature of Turner syndrome. We have also found that the mouse homo log of PHOG is autosomal, which may help to explain the lack of a grow th abnormality in mice with monosomy X.