A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators

Deletion of the distal short arm of chromosome 9 (9p) has been reported in a number of cases to be associated with gonadal dysgenesis and XY sex rever sal, suggesting that this region contains one or more genes required in two copies for normal testis development, Recent studies have greatly narrowed the interval containing this putative autosomal testis-determining gene(s) to the distal portion of 9p24.3. We previously identified DMRT1, a human g ene with sequence similarity to genes that regulate the sexual development of nematodes and insects. These genes contain a novel DNA-binding domain, w hich we named the DM domain, DMRT1 maps to 9p24.3 and in adults is expresse d specifically in the testis, We have investigated the possible role of DM domain genes in 9p sex reversal. We identified a second DM domain gene, DMR T2, which also maps to 9p24.3, We found that point mutations in the coding region of DMRT1 and the DM domain of DMRT2 are not frequent in XY females. We showed by fluorescence in situ hybridization analysis that both genes ar e deleted in the smallest reported sex-reversing 9p deletion, suggesting th at gonadal dysgenesis in Sp-deleted individuals might be due to combined he mizygosity of DMRT1 and DMRT2.