title: Biochemical and molecular analysis in a patient with the severe form of Hunter syndrome after bone marrow transplantation.
abstract: Hunter syndrome (mucopolysaccharidosis type II, or MPS II) results from a deficiency of iduronate-2-sulfatase (IDS) activity due to a primary genetic defect in the X-chromosomal iduronate-2-sulfatase gene. We have studied a 10-year-old male, diagnosed with Hunter syndrome at age 2 years, who underwent bone marrow transplantation (BMT) at age 5 years. To evaluate the metabolic effect of BMT, biochemical and enzymatic studies were performed. Urinary glycosaminoglycans (GAGs) were quantitated, and iduronate-2-sulfatase activity was measured in serum, leukocytes, and liver homogenates. Decreased urinary glycosaminoglycan excretion and increased iduronate-2-sulfatase activity in serum and leukocytes were observed. Furthermore, molecular analysis was performed using reverse transcriptional polymerase chain reaction (RT-PCR) sequencing and restriction enzyme assay. The patient was found to have a novel nonsense mutation, L279X (TTA to TGA) in exon 6 of the IDS gene, inherited from his mother. A comparison of the DNA contents of cultured skin fibroblasts prior to BMT with leukocyte DNA after BMT showed coexisting host mutant and donor normal alleles in post-BMT leukocyte DNA. We postulate that the L279X mutation is a severe disease-causing mutation for Hunter syndrome.
authors.affiliation: Laboratory of Medical Genetics, University of Alabama at Birmingham, Ohio 35294-0017, USA.
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: J N
authors.initials: JN
authors.lastname: Thompson
authors.forename: G
authors.initials: G
authors.lastname: Hug
authors.forename: P
authors.initials: P
authors.lastname: Huffman
authors.forename: G
authors.initials: G
authors.lastname: Chuck
mesh_terms: D016026:Bone Marrow Transplantation; D002648:Child; D006801:Humans; D008297:Male; D016532:Mucopolysaccharidosis II / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction