Carrier detection in Wiskott-Aldrich syndrome: combined use of M27 beta for X-inactivation studies and as a linked probe

Abstract

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder with no clinical or immunologic abnormalities in carrier females. The defective gene has been localized to proximal Xp. Carrier females have nonrandom use of the X chromosome in granulocytes, lymphocytes, and monocytes. We have used the probe M27 beta, which detects both a variable number tandem repeat polymorphism and methylation differences between the active and inactive X chromosome, in the investigation of families referred for genetic counseling. M27 beta detects the locus DXS255, which is tightly linked to WAS. As the probe that is used for investigation of X-inactivation patterns is also linked to the disease locus, it is possible to assign phase in families where this could not be done by conventional use of linked probes. The mothers of four isolated male cases had nonrandom use of the X chromosome. A new mutation was identified in one family with two affected males.