CLINICAL STUDY Female gonadal development in XX patients with distal 9p monosomy

Objective: A sex determining gene(s) has been mapped to a,700 kb region distal to the exons of DMRT1 on 9p. The aim of this study was to examine 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 hormone (GnRH) tests. Hemizygosity for the sex determining region was examined by fluorescence in situ hybridisation and microsatellite analyses for a total of 17 loci on distal 9p. Results: GnRH tests indicated mild gonadotrophin hyper responses in both cases (case 1: follicle stimulating hormone 9.2!22.7 IU/l, luteinising hormone 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 hemizygosity for the 9p sex determining region in both cases. Conclusions: The results, in conjunction with previous reports describing sex development in XX and XY patients hemizygous for the 9p sex determining region, imply that haploinsufficiency of the 9p sex determining gene(s) primarily hinders the formation of the indifferent gonad, leading to a wide range of testicular or ovarian development. European Journal of Endocrinology 145 613–61