CLONING AND CHARACTERIZATION OF THE HUMAN CHOROIDEREMIA GENE

Positional cloning has previously resulted in the identification of a gene which is disrupted by deletions in patients with the classic chor oideremia (CHM) phenotype. More subtle mutations had been identified i n 4 exons of the 3' portion but not elsewhere in the CHM gene. We have now isolated and characterized the complete open reading frame of the CHM gene and determined its exon - intron structure. The CHM gene enc odes a protein of 653 amino acids, which is highly homologous to the m ouse and rat CHM proteins, and, to a slightly lesser extent, to the hu man CHM-like (CHML) protein. The open reading frame (ORF) of the human CHM gene consists of 15 exons, spanning at least 150 kb of Xq21.2, an d it is possible that there is an additional exon corresponding to the 5' non-coding region of the gene. Cloning of the 5' end of the CHM ge ne and the elucidation of its intron - exon structure enabled us to lo calize the X-chromosomal breakpoint in a CHM female with an X;7 transl ocation between exons 3 and 4.