MUTATION SPECTRUM IN THE CHM GENE OF DANISH AND SWEDISH CHOROIDEREMIAPATIENTS

The recent isolation of the complete open reading frame of the choroid eremia (CHM) gene and the characterization of the exon - intron bounda ries has paved the way to mutation detection in patients with classica l choroideremia. We have performed mutation screening in patients from 15 Danish and Swedish families by using Southern blot hybridization a nd the polymerase chain reaction single-strand conformation polymorphi sm (PCR-SSCP) technique. Causative mutations in the CHM gene were dete cted in at least 12 families, indicating that a substantial part of th e mutations can be identified by this approach. In four of these famil ies deletions of different sizes were found. Thus, in one patient, the deletion resulted in the absence of only one exon, while in another t he deletion comprised the entire CHM gene. Mapping of the deletion end points in these four patients and in another 11 male patients with siz eable deletions enabled us to construct a very detailed map of interva ls 2 and 3 of Xq21. In the remaining 11 Danish and Swedish families at least 8 causative mutations were found by PCR - SSCP analysis and dir ect sequencing. Interestingly, all CHM gene mutations detected thus fa r in choroideremia patients give rise to the introduction of a prematu re stop codon.