Pn. Li et al., BIOCHEMICAL AND MOLECULAR ANALYSIS IN A PATIENT WITH THE SEVERE FORM OF HUNTER SYNDROME AFTER BONE-MARROW TRANSPLANTATION, American journal of medical genetics, 64(4), 1996, pp. 531-535
Hunter syndrome (mucopolysaccharidosis type II, or MPS II) results fro
m a deficiency of iduronate-2-sulfatase (IDS) activity due to a primar
y genetic defect in the X-chromosomal iduronate-2-sulfatase gene. We h
ave studied a 10-year-old male, diagnosed with Hunter syndrome at age
2 years, who underwent bone marrow transplantation (BMT) at age 5 year
s. To evaluate the metabolic effect of BRIT biochemical and enzymatic
studies were performed, Urinary glycosaminoglycans (GAGs) were quantit
ated, and iduronate-2-sulfatase activity was measured in serum, leukoc
ytes, and liver homogenates. Decreased urinary glycosaminoglycan excre
tion and increased iduronate-2-sulfatase activity in serum and leukocy
tes 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 n
onsense mutation, L279X (TTA to TGA) in exon 6 of the IDS gene, inheri
ted from his mother. A comparison of the DNA contents of cultured skin
fibroblasts prior to BRIT with leukocyte DNA after BRIT showed coexis
ting host mutant and donor normal alleles in post-BRIT leukocyte DNA.
We postulate that the L279X mutation is a severe disease-causing mutat
ion for Hunter syndrome. (C) 1996 Wiley-Liss, Inc.