FAILURE OF TESTICULAR DEVELOPMENT ASSOCIATED WITH A REARRANGEMENT OF 9P24.1 PROXIMAL TO THE SNF2 GENE

In 46,XY individuals, testes are determined by the activity of the SRY gene (sex-determining region Y), located on the short arm of the Y ch romosome. The other genetic components of the cascade that leads to te stis formation are unknown and may be located on the X chromosome or o n the autosomes. Evidence for the existence of several loci associated with failure of male sexual development is indicated by reports of 46 ,XY gonadal dysgenesis associated with structural abnormalities of the X chromosome or of autosomes (chromosomes 9, 10, 11 and 17). In this report, we describe the investigation of a child presenting with multi ple congenital abnormalities, mental retardation and partial testicula r failure. The patient had a homogeneous de novo 46,XY,inv dup(9)(pter -->p24.1::p21.1-->p23.3::p24.1-->qter) chromosome complement. No delet ion was found by either cytogenetic or molecular analysis. The SRY gen e and DSS region showed no abnormalities. Southern blotting dosage ana lysis with 9p probes and fluorescent in situ hybridisation data indica ted that the distal breakpoint of the duplicated fragment was located at 9p24.1, proximal to the SNF2 gene. We therefore suggest that a gene involved in normal testicular development and/or maintenance is prese nt at this position on chromosome 9.