PRENATAL IN-SITU HYBRIDIZATION TEST FOR DELETED STEROID SULFATASE GENE

X-linked ichthyosis results from steroid sulfatase (STS) deficiency; 9 0% of affected patients have a complete deletion of the entire 146 kb STS gene on the distal X chromosome short arm (Xp22.3). In these famil ies prenatal diagnosis and carrier testing can be completed in 2 days by hybridizing simultaneously 2 different cosmid probes labeled with f luorescein or Texas red and counterstaining interphase nuclear DNA wit h DAPI. An STS gene probe labeled with Texas red hybridizes specifical ly to the steroid sulfatase gene on the X chromosome. A second flankin g probe labeled with fluorescein hybridizes to both the normal Y chrom osome and normal and STS deleted X chromosomes. In this fashion the in terphase nuclei of normal males, affected males, normal females, and c arrier females can be distinguished unambiguously. Because normal male s and carrier females each show two yellow-green fluorescein spots and one Texas red STS spot, use of this test prenatally requires determin ing fetal sex independently with repetitive X and Y chromosome-specifi c probes. This procedure can be used with lymphocytes, direct and cult ured chorionic villus cells, direct and cultured amniocytes, and fibro blasts. Similar methods are anticipated to be useful for rapid diagnos tic assessment of other aneuploid gene disorders. (C) 1993 Wiley-Liss, Inc.