MAPPING OF THE DISTAL BOUNDARY OF THE X-INACTIVATION CENTER IN A REARRANGED X-CHROMOSOME FROM A FEMALE EXPRESSING XIST

A female patient with primary amenorrhea, immature secondary sexual ch aracteristics, and tall stature was found to have a normal X chromosom e and a rearranged X [rea(X)] chromosome that resembled an 'isochromos ome' Xp, but retained the proximal portion of Xq. The rea(X) was inter preted as rec(X)dup p,inv(X)(p11.4q13). Replication studies demonstrat ed that the rea(X) was always the late-replicating and, therefore, pre sumably inactive X chromosome, which must contain the X-inactivation c enter. Consistent with this interpretation, fluorescence in situ hybri dization demonstrated that the rea(X) retained the XIST gene, and reve rse transcription polymerase chain reaction analysis showed that XIST was expressed in the patient's cells. By fluorescence in situ hybridiz ation with previously mapped probes, the breakpoint of the rea(X) was located within an approximately 500-kb region located approximately 20 0 to 700 kb distal to the XIST locus. This is the closest breakpoint d istal to XIST in an inactivated X chromosome and, therefore, defines a new distal boundary for the X-inactivation center in humans.