Deletions in patients with classical choroideremia vary in size from 45 kb to several megabases

Making use of the p1bD5 probe (DXS165), we have isolated several markers from the choroideremia locus by chromosomal jumping, preparative field-inversion gel electrophoresis, and cloning of a deletion junction fragment. With these clones we were able to identify and characterize eight deletions in 69 choroideremia patients investigated. The deletions are heterogeneous, in both size and location. The smallest deletion (patient LGL1134) comprises approximately 45 kb of DNA, whereas the largest ones (patients 25.6 and LGL2905) span a DNA segment of at least 5 megabases, which is comparable in size to the smallest deletion detected in a TCD patient (patient XL45) showing a complex phenotype. The TCD deletions encompass variable parts of 150-200-kb DNA segment that is flanked by p1bD5 (DXS165) at the centromeric side and by pZ 11 at the telomeric side. The deletions in patients 33.1, LGL1101, and LGl1134 do not span a translocation breakpoint which was previously mapped on the X chromosome of a female with TCD. The clones isolated from the TCD locus are valuable diagnostic markers for deletion analysis of patients or carrier females. In addition, they should be useful for the isolation of expressed sequences that are part of the TCD gene.