WISKOTT-ALDRICH SYNDROME - CELLULAR IMPAIRMENTS AND THEIR IMPLICATION FOR CARRIER DETECTION

  • 1 January 1980
    • journal article
    • research article
    • Vol. 56  (6) , 1048-1054
Abstract
A family in which 2 male siblings were affected with Wiskott-Aldrich syndrome (WAS) was studied using G-6-PD [glucose-6-phosphate dehydrogenase] isoenzymes as an X-linked marker in order to investigate the nature of cellular abnormalities. Isolated peripheral blood cell types from the doubly heterozygous mother of the affected males seemingly failed to express the G-6-PD allele in cis position with the WAS allele, while her cultured skin fibroblasts expressed both G-6-PD alleles. A histogram analysis of platelet size revealed a single population of abnormally small platelets in the affected propositus, whereas the heterozygous mother had no appreciable small platelet subpopulation. In vitro culture of hemopoietic progenitor cells of the heterozygous mother showed that the majority of progenitor cells did not express the WAS allele. A small number of cells expressing the G-6-PD type linked with the WAS allele were detected. The proportion of the latter progenitors was significantly higher among more primitive progenitors (those giving rise to later appearing colonies). Selection against cells expressing the Wiskott-Aldrich defect apparently occurs in the hemopoietic system of the heterozygous female and offers a possible means of carrier detection in some women. Linkage studies in this family revealed 1 example of probable recombination between the loci for WAS and G-6-PD among 3 informative subjects, suggesting that these 2 loci may not be closely linked on the X-chromosome.