Hunter syndrome: isolation of an iduronate-2-sulfatase cDNA clone and analysis of patient DNA.

• DOI: 10.1073/pnas.87.21.8531
• Publication Date: 2006-05-31T11:30:10Z
• Authors: P J Wilson; C P Morris; D S Anson; T Occhiodoro; J Bielicki; P R Clements; J J Hopwood
• Keywords: 0303 health sciences; Base Sequence; Molecular Sequence Data; Restriction Mapping; DNA; Iduronate Sulfatase; 3. Good health; 03 medical and health sciences; Liver; Sequence Homology, Nucleic Acid; Animals; Humans; Amino Acid Sequence; Cloning, Molecular; Oligonucleotide Probes; Gene Library; Mucopolysaccharidosis II

Iduronate 2-sulfatase (IDS, EC 3.1.6.13) is required for the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations causing IDS deficiency in humans result storage these glycosaminoglycans Hunter syndrome, an X chromosome-linked disease. We have isolated sequenced a 2.3-kilobase cDNA clone coding entire sequence human IDS. Analysis deduced 550-amino acid precursor indicates that has 25-amino amino-terminal signal sequence, followed by 8 amino acids are removed from proprotein. An internal proteolytic cleavage occurs to produce mature present liver shown contain 42-kDa polypeptide N-terminal 14-kDa polypeptide. The strong homology with other sulfatases (such as sea urchin arylsulfatase, arylsulfatases A, B, C, glucosamine 6-sulfatase), suggesting comprise evolutionarily related family genes arose gene duplication divergent evolution. greater each than non-arylsulfatases (IDS 6-sulfatase). detected RNA species 5.7, 5.4, 2.1, 1.4 kilobases placental revealed structural alterations gross deletions many clinically severe syndrome patients studied.