A HUMAN HOMOLOG OF THE DROSOPHILA-MELANOGASTER SLUGGISH-A (PROLINE OXIDASE) GENE MAPS TO 22Q11.2, AND IS A CANDIDATE GENE FOR TYPE-I HYPERPROLINEMIA

We have cloned the complete coding region for a human homologue of the Drosophila melanogaster sluggish-A and yeast PUT1 genes, previously s hown to encode proline oxidase activity in these organisms. The predic ted 516-residue human protein shows strong homology (51% amino acid se quence identity) to the D. melanogaster-protein, indicating that this new human gene may encode proline oxidase. Northern analysis shows tha t the gene is expressed in human lung, skeletal muscle and brain, to a lesser extent in heart and kidney, and weakly in liver, placenta and pancreas. The gene was mapped by fluorescence in situ hybridization an d by in situ hybridization with a [H-3]-labelled DNA probe to chromoso me 22q11.2, a region previously implicated in type-I hyperprolinaemia in a case of CATCH 22 syndrome, a contiguous gene deletion syndrome in volving 22q11. Taken together, the evidence indicates that this new hu man gene is a good candidate gene for type-I hyperprolinaemia. In view of the neurological phenotype of the D. melanogaster sluggish-A mutan t, it is of interest that schizophrenia and bipolar disorder susceptib ility genes also map in this region.