MOLECULAR CHARACTERIZATION OF TINY RING X-CHROMOSOMES FROM FEMALES WITH FUNCTIONAL X-CHROMOSOME DISOMY AND LACK OF CIS-X INACTIVATION

Small ring X chromosomes were first described in mosaic karyotypes of females with the relatively benign phenotype of Turner syndrome. The p resence of these rings in association with more severe phenotypes incl uding mental retardation has raised the possibility that they lack seq uences necessary for X chromosome inactivation, specifically genes wit hin the X inactivation center (XIC) essential for cia X-inactivation. We recently showed that ring X chromosomes ascertained because of the severe phenotype do not express XIST, a candidate for the relevant gen e, and that they are in fact active chromosomes. We now report studies of the genetic content of 11 of these ring X chromosomes (9 associate d with severe phenotypes). Our results indicate that these chromosomes contain contiguous segments of DNA and have variable proximal and dis tal breakpoints and some include mainly long arm or mainly short arm s equences. As expected for ring chromosomes, they lack telomeric sequen ces. Many of the ring chromosomes lack the XIST locus, consistent with XIST being necessary for cis inactivation. However, the breakpoints i n four ring chromosomes that have XIST sequences but do not express XI ST suggest that other sequences within the XIC distal to XIST as it is now defined are also needed. (C) 1995 Academic Press, Inc.