Hunter disease is an X-linked recessive mucopolysaccharide storage disorder 
caused by iduronate-2-sulfatase deficiency and is rare in females. We describe 
here findings in a girl with Hunter disease of the severe type. She had a normal 
karyotype but a marked deficiency of iduronate-2-sulfatase activity in 
lymphocytes and cultured fibroblasts. In a sequence analysis of the 
iduronate-2-sulfatase gene, evidence was obtained for the R468Q (G1403 to A) 
mutation, a common one in Hunter disease. RT-PCR showed her cDNA to represent 
only the R468Q allele, although at the genomic level she was a heterozygote with 
one normal allele. Her brother had the R468Q mutation, and their mother was a 
carrier of this mutation. The fusion products of CHO (TG(R),Neo(R)) with 
patient's fibroblasts cultured in HAT/G418 selective medium, carried only the 
maternal allele. However, in genomic DNA from the patient's fibroblasts, only 
the paternal allele of the androgen receptor gene, a gene subjected to 
differential methylation of the inactive X-chromosome, was methylated. These 
findings strongly suggest that the severe form of Hunter disease in this girl 
was the result of selective expression of the maternal allele carrying the 
missense mutation R468Q, which in turn resulted from skewed X inactivation of 
the paternal nonmutant X chromosome.