MUTATION ANALYSIS IN THE IDURONATE-2-SULFATASE GENE IN 43 JAPANESE PATIENTS WITH MUCOPOLYSACCHARIDOSIS TYPE-II (HUNTER-DISEASE)

Our series of studies on Hunter disease in Japanese patients showed al lelic heterogeneity of IDS gene mutations, genotype/phenotype correlat ion and racial differences in distribution of mutations. Twenty-five d ifferent small mutations have been characterized. Small mutations in t he Japanese population an widely distributed through the IDS gene, alt hough some mutations were unevenly concentrated on exon 5 (28%) and on exon 9 (24%). Mutations were seen at the same codon 468 in exon 9 in 5 patients. These findings are in good agreement with data on other et hnic groups. Two unique mutations linked to a severe phenotype were ap parently associated with aberrant splicings; one was a point mutation within exon 3 (P86L), partially activating a cryptic splice acceptor s ite at 28 bp downstream from the mutation site within exon 3 and produ cing a 44-base truncated mRNA, and the other was a point mutation at t he consensus sequence of the splice donor site of intron 2, causing ex on 2 skipping.