Female gonadal development in XX patients with distal 9p monosomy

Objective: A sex determining gene(s) has been mapped to a similar to 700 kb region distal to the exons of DMRT1 on 9p. The aim of this study was to ex amine gonadal developmental status in XX patients hemizygous for the 9p sex determining region. Design: Clinical and molecular studies were performed in an 8-year-old girl with 46,XX,del(9)(p22) (case 1) and in a 2-year-old girl with 46,XX,del(9) (p23) (case 2). Methods: Ovarian function status was assessed by gonadotrophin-releasing ho rmone (GnRH) tests. Hemizygosity for the sex determining region was examine d by fluorescence in situ hybridisation and microsatellite analyses for a t otal of 17 loci on distal 9p. Results: GnRH tests indicated mild gonadotrophin hyper responses in both ca ses (case 1: follicle stimulating hormone 9.2 --> 22.7 IU/l, luteinising ho rmone 0.7 --> 16.6 IU/l; case 2: follicle stimulating hormone 7.6 --> 38.2 IU/l, luteinising hormone 0.6 --> 9.4 IU/l). Molecular studies showed hemiz ygosity for the 9p sex determining region in both cases. Conclusions: The results, in conjunction with previous reports describing s ex development in XX and XY patients hemizygous for the 9p sex determining region, imply that haploinsufficiency of the 9p sex determining gene(s) pri marily hinders the formation of the indifferent gonad, leading to a wide ra nge of testicular or ovarian development.