Familial X-chromosome inactivation (XCI) skewing was investigated in a family in 
which a female mucopolysaccharidosis type II (MPS II) (Hunter syndrome, an 
X-linked genetic disease) occurred. Among eight related females aged under 60 
years from three generations who were tested, four revealed a non-random pattern 
of XCI. Detailed genetic analysis failed to find mutations in genes that were 
previously reported as important for the XCI process. Haplotype analysis 
excluded linkage of non-random XCI with genes localized on the X-chromosome. We 
propose that analysis of the XCI pattern should be taken into consideration when 
assessing risk factors for X-linked recessive genetic disorders.