2 DISTINCT DELETIONS IN THE IDS GENE AND THE GENE-W - A NOVEL TYPE OFMUTATION ASSOCIATED WITH THE HUNTER-SYNDROME

A novel mutation has been identified in a patient with the Hunter synd rome (mucopolysaccharidosis type II), in whom the disorder is associat ed with two distinct deletions separated by 30 kb. The deletions were characterized by Southern blot and PCR analyses, and the nucleotide se quences at both junctions were determined, The first deletion, corresp onding to a loss of 3152 bp of DNA, included exons 5 and 6 of the idur onate-2-sulfatase (IDS) gene. The second deletion was 3603 bp long and included exons 3 and 4 of gene W which is located in the DXS466 locus telomeric of the IDS gene, Both deletions are the result of nonhomolo gous (illegitimate) recombination events between short direct repeats at the deletion breakpoints. An interesting finding was the presence o f the heptamer sequence 5'-TACTCTA-3' present at both deletion junctio ns, suggesting that this motif might be a hot spot for recombination. We propose that the double deletion is the result of homology-associat ed nonhomologous recombinations caused by the presence of large duplic ated regions in Xq27.3-q28. (C) 1997 Academic Press.