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.