title: The usefulness of X-linked polymorphic loci as gene markers to track X allele and chimerism in a post-allogeneic peripheral blood stem cell transplant patient with Wiskott-Aldrich syndrome.
abstract: Wiskott-Aldrich syndrome (WAS), an X-linked recessive disorder, is characterized by progressive T-cell immunodeficiency. Laboratory findings generally demonstrate reduced response to T-cell mitogens, markedly decreased serum concentration of IgM, and thrombocytopenia with small platelet volume. Allogeneic HLA-matched sibling bone marrow transplantation (BMT) can correct this disorder. We report the usefulness of X-linked polymorphic loci to detect X-allele gene tracking among WAS siblings and chimerism between a pre- and post-allogeneic matched sibling peripheral blood stem cell transplantation (PBSCT). A 3 1/2 year old boy with clinical and laboratory findings consistent with WAS underwent allogeneic matched sibling PBSCT. We used BclI restriction fragment length polymorphism (RFLP) of intron 18 of factor VII gene and MseI RFLP of the 5' flanking region of factor IX gene to detect X-allele gene tracking among siblings and family members and chimerism in patients between pre-and post-allogeneic matched sibling PBSCT. We were able to demonstrate that determination of BclI and MseI RFLP can be employed to recognize the difference in X-allele genes between the recipient and donor for allogeneic matched sibling PBSCT. The authors also were able to demonstrate that these polymorphic loci can detect full chimerism of donor hematopoietic cells in recipient blood after allogeneic PBSCT. This finding was correlated with improvement of post-PBSCT clinical and laboratory findings. BclI and MseI RFLP associated with X-chromosome can effectively track X-allele, detect carrier state, and demonstrate the different X-allele among male siblings, and chimerism of hematopoietic cells between donors and recipients in a setting of allogeneic matched sibling BMT or PBSCT for X-linked hereditary diseases such as Wiskott-Aldrich syndrome.
authors.affiliation: Research Center, Faculty to Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: W
authors.initials: W
authors.lastname: Sasanakul
authors.forename: S
authors.initials: S
authors.lastname: Hongeng
authors.forename: A
authors.initials: A
authors.lastname: Chuansumrit
authors.forename: W
authors.initials: W
authors.lastname: Chaiyaratana
authors.forename: S
authors.initials: S
authors.lastname: Pakakasama
authors.forename: P
authors.initials: P
authors.lastname: Hathirat
mesh_terms: D002675:Child, Preschool; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics* / Q000628:therapy*; D014960:X Chromosome