Detection of lymphocytes and granulocytes expressing the mutant WASP message in carriers of Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease caused by m utations in the recently identified WAS protein gene (WASP). In some X-link ed genetic disorders skewed X-inactivation has been observed in all cell po pulations or some specific cell lineages of female carriers, Recently, fema le carriers of WAS were also revealed to present skewed X-inactivation patt erns at the haemopoietic stem cell le level. However, it is not clear if al l haematological cells expressing the mutant WASP allele are eliminated in WAS carriers. By reverse transcription PCR methods, we studied 14: WAS carr iers from 10 different families to assess whether brood cells expressing th e mutant WASP message were present in their peripheral brood. The mutations of each WAS patient were known and carrier diagnosis of their female famil y members was performed using specific mutation analysis. We detected circu lating lymphocytes and granulocytes expressing the mutant WASP message in m ost of the WAS carriers, nevertheless they showed skewed X-chromosomal inac tivation patterns. Interestingly, the presence of blood cells expressing th e mutant WASP message seemed to correlate to the WASP genotype and the age of the carriers.