NONRANDOM INACTIVATION OF THE X-CHROMOSOME IN EARLY LINEAGE HEMATOPOIETIC-CELLS IN CARRIERS OF WISKOTT-ALDRICH SYNDROME

The Wiskott-Aldrich syndrome (WAS) is an X-linked (Xp11.22) recessive immunodeficiency syndrome characterized by susceptibility to opportunistic and pyogenic infections. thrombocytopenia, and eczema. Previous studies of obligate carriers of WAS documented that nonrandom inactivation of the X chromosome carrying the defective gene is observed in all peripheral blood cells, The existence of both abnormal platelets and lymphocytes is consistent with a defect that affects early hematopoietic precursors. We isolated CD34(+) hematopoietic progenitor cells collected from obligate carriers of WAS by apheresis and used polymerase chain reaction analysis of a polymorphic variable number of repeats (VNTR) within the X-linked androgen receptor to document nonrandom inactivation. These data show that nonrandom inactivation of the X-chromosome in WAS-obligate carriers occurs early during hematopoietic differentiation. (C) 1995 by The American Society of Hematology.