Novel mutations, no detectable mRNA and familial genetic analysis of the Wiskott-Aldrich syndrome protein gene in six Japanese patients with Wiskott-Aldrich syndrome

The Wiskott-Aldrich syndrome (WAS) is a primary X-linked immunodeficiency d isease caused by mutations of the Wiskott-Aldrich syndrome protein (WASP) g ene. The present molecular studies of six Japanese WAS patients identified five different mutations of WASP, including two novel mutations (45delG, 39 5insGGAGAT), the latter appearing to have occurred de novo. Familial carrie rs were detected by polymerase chain reaction-single strand conformational polymorphism analysis, restriction enzyme digestion and direct sequencing o f PCR products. Neither mRNA nor the protein product were detectable in any of the patients, while various amounts of WASP protein were expressed in c arriers, normal controls, haematopoietic cell lines of all lineages and in one patient after receiving allogeneic bone marrow transplantation. Conclusion Genetic and protein analysis is useful in the definite diagnosis and follow up of Wiskott-Aldrich syndrome patients and in carrier detectio n, especially of atypical or sporadic patients.