Molecular analysis in 23 Hunter syndrome families.

Hunter syndrome is an X-linked storage disease caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). Both the cDNA and the genomic structure of the gene have been determined. We have used Southern blotting and single-strand conformation polymorphism (SSCP) analysis of the 9 IDS exons and boundaries to detect the molecular defects in the genes of 23 unrelated Hunter syndrome families from Argentina, Belgium, France, Spain, Uruguay and Zaire. In 2 patients deletions involving several axons of the gene were found. Different missense mutations were present in exon 2 (1 patient), exon 3 (2), exon 8 (2) and exon 9 (4). Three of the mutations in exon 9 were affecting the same codon resulting in amino acid changes E521* E521K and E521V. Incorrect splicing of exon 6 (1 patient), exon 7 (1) and exon 8 (4) caused Hunter syndrome, while premature translation termination resulted from small deletions or insertions, or nonsense mutations in 6 patients. In all families the mutation was identified by the methodology used. The molecular data obtained can be used for prenatal diagnosis, but they especially prove valuable for carrier detection in female relatives of Hunter patients, in whom enzyme determinations are non-conclusive.