SHOT, A SHOX-RELATED HOMEOBOX GENE, IS IMPLICATED IN CRANIOFACIAL, BRAIN, HEART, AND LIMB DEVELOPMENT

Deletion of the SHOX region on the human sex chromosomes has been show n to result in idiopathic short stature and proposed to play a role in the short stature associated with Turner syndrome. We have identified a human paired-related homeobox gene, SHOT, by virtue of its homology to the human SHOX and mouse OG-12 genes. Two different isoforms were isolated, SHOTa and SHOTb, which have identical homeodomains and share a C-terminal 14-amino acid residue motif characteristic for craniofac ially expressed homeodomain proteins. Differences between SHOTa and b reside within the N termini and an alternatively spliced exon in the C termini. In situ hybridization of the mouse equivalent, OG-12, on sec tions from staged mouse embryos detected highly restricted transcripts in the developing sinus venosus (aorta), female genitalia, diencephal on, mes- and myelencephalon, nasal capsula, palate, eyelid, and in the limbs. SHOT was mapped to human chromosome 3q25-q26 and OG-12 within a syntenic region on chromosome 3. Based on the localization and expre ssion pattern of its mouse homologue during embryonic development, SHO T represents a candidate for the Cornelia de Lange syndrome.