INVERSION OF THE IDS GENE RESULTING FROM RECOMBINATION WITH IDS-RELATED SEQUENCES IS A COMMON-CAUSE OF THE HUNTER SYNDROME

We have recently described the identification of a second IDS locus (I DS-5) located within 90 kb telomeric of the IDS gene (Bondeson al al. submitted). Here, we show that this region is involved in a recombinat ion event with the IDS gene in about 13% of patients with the Hunter s yndrome. Analysis of the resulting rearrangement at the molecular leve l showed that these patients have suffered a recombination event that results in a disruption of the IDS gene in intron 7 with an inversion of the intervening DNA. Interestingly, all of the six cases with a sim ilar type of rearrangement showed recombination between intron 7 of th e IDS gene and sequences close to exon 3 at the IDS-2 locus implying t hat these regions are hot spots for recombination. Analysis by nucleot ide sequencing showed that the inversion is caused by recombination be tween homologous sequences present in the IDS gene and the IDS-2 locus . No detectable deletions or insertions were observed as a result of t he recombination event. The results in this study have practical impli cations for diagnosis of the Hunter syndrome.