DXS165 detects a translocation breakpoint in a woman with choroideremia and a de novo X; 13 translocation.

The search for the gene for choroideremia (MIM 30310), a rare retinal dystrophy, has been of great interest due to the existence of several choroideremia patients with well-defined structural chromosome aberrations, thus providing the basis for a reverse genetics approach to the isolation of this disease gene. This report details our molecular studies of a woman with choroideremia and a de novo X; 13 translocation. Pulsed-field gel electrophoresis using a contour-clamped homogeneous electric field apparatus has allowed detection of the translocation breakpoint with the anonymous DNA marker p1bD5 (DXS165) and the mapping of this probe to within 120 kb of the breakpoint. In addition, we have used this probe to isolate a clone (pCH4) from a 100-kb jumping library which has crossed a rare-cutting restriction site (XhoI) between DXS165 and the choroideremia gene and detects the translocation breakpoint using this enzyme. Although DXS165 lies within 120 kb of the breakpoint and Cremers et al. (1987, Clin. Genet. 32: 421-423; 1989, PNAS 86: 7510-7514) have detected deletions of DXS165 in 3 of 30 choroideremia probands, we have detected no deletions of this marker or of pCH4 in 42 unrelated probands with this retinal disease.