Subject(s)
Glycosaminoglycans/urine , Infant, Newborn/urine , Age Factors , Birth Weight , Creatinine/urine , Female , Follow-Up Studies , Gestational Age , Humans , Infant , Male , Mucopolysaccharidoses/diagnosis , Mucopolysaccharidoses/urine , Mucopolysaccharidosis II/urine , Mucopolysaccharidosis III/urine , Mucopolysaccharidosis VII/urineABSTRACT
Hunter disease is an X-linked recessive disorder caused by a deficiency of iduronate-2-sulfatase activity. We describe a pair of brother/sister siblings with a typical feature of Hunter disease (mucopolysaccharidosis type II). They had normal karyotypes but a marked deficiency of iduronate-2-sulfatase activity in both lymphocytes and fibroblasts. The molecular analysis of the iduronate-2-sulfatase gene revealed the R468L(G1403-->T) substitution in their genes. Although the sister's genomic DNA was heterozygous for the mutant allele, the sister's cDNA was found to be homogeneous for this mutation. The mother was found to be a heterozygote. The analysis of X chromosome inactivation by comparison of the methylation patterns of the androgen-receptor (AR) gene which was isolated from the sister's fibroblasts and leucocytes revealed a skewed X chromosome inactivation of the paternal allele. These findings indicate that a skewed X chromosome inactivation of the paternal gene and a point mutation in the maternal gene were responsible for the lack of iduronate-2-sulfatase activity in the sister.
