Abstract

Mucopolysaccharidosis type II (Hunter syndrome) is an X linked lysosomal storage disorder resulting from heterogeneous mutations in the iduronate-2-sulphatase (IDS) gene. To detect IDS gene mutations, direct sequencing of IDS cDNA fragments coupled with assays on IDS genomic amplicons was applied to 18 unrelated patients with MPS II. Seventeen mutations were detected from the 18 patients including seven missense mutations (S71R, A82E, A85T, R88C, R468W, R468Q, and E521V), five deletions (ΔR95, 383delAT, 596delAACA, 1148delC, and 1216delCT), two insertions (208insC and 1063insA), two splicing mutations (1006+5g→c in intron 7, 1122C→T in exon 8), and an intragenic deletion of IDS exons 4, 5, 6, and 7. Nine of the small mutations were novel mutations. Mutation 596delAACA was detected in two unrelated patients. The mutation in intron 7 was found to cause aberrant splicing and resulted in a 22 bp insertion into its mRNA transcript. The intragenic deleted IDS gene expressed two aberrant mRNA transcripts consisting of exons 1-2-8-9 and 3-8-9. Analysis of mutations A85T, R88C, R468Q, R468W, and 438C/T found no polymorphism for the four missense mutations but about 36% heterozygosity for the 438C/T silent mutation. These results provide further evidence of mutational heterogeneity for MPS II. Also, underlying sequence directed mutagenesis mechanisms for some recurrent mutations in the IDS gene were proposed.