J Korean Med Sci.  2009 Aug;24(4):751-754. 10.3346/jkms.2009.24.4.751.

Phenotypic and Genotypic Correction of WASP Gene Mutation in Wiskott-Aldrich Syndrome by Unrelated Cord Blood Stem Cell Transplantation

• Lee YH
• Lim YJ
• Shin SA
• Song CH
• Jo EK
• Jung JA
• Lee HB

• KMID: 1779216
• DOI: http://doi.org/10.3346/jkms.2009.24.4.751

Abstract

We present two cases of Wiskott-Aldrich syndrome (WAS), in which nonsense mutations in the WASP gene were corrected phenotypically as well as genotypically by unrelated cord blood stem cell transplantation (CBSCT). Two male patients were diagnosed with WAS at the age of 5-month and 3-month and each received unrelated CBSCT at 16-month and 20-month of age, respectively. The infused cord blood (CB) units had 4/6 and 5/6 HLA matches and the infusion doses of total nucleated cells (TNC) and CD34+ cells were 6.24x10(7)/kg and 5.08x10(7)/kg for TNC and 1.33x10(5)/kg and 4.8x10(5)/kg for CD34+ cells, for UPN1 and UPN2, respectively. Complete donor cell chimerism was documented by variable number tandem repeat (VNTR) with neutrophil engraftment on days 31 and 13 and platelets on days 58 and 50, respectively. Immunologic reconstitution demonstrated that CBSCT resulted in consistent and stable T-, B-, and NK-cell development. Flow cytometric analysis for immunologic markers and sequence analysis of the WASP gene mutation revealed a normal pattern after CBSCT. These cases demonstrate that CBs can be an important source of stem cells for the phenotypical and genotypical correction of genetic diseases such as WAS.

Keyword

Wiskott-Aldrich Syndrome; WASP; Unrelated Cord Blood Stem Cell Transplantation

MeSH Terms

*Cord Blood Stem Cell Transplantation
Follow-Up Studies
Genotype
HLA Antigens/immunology
Humans
Infant
Male
Mutation
Phenotype
Sequence Analysis
Wiskott-Aldrich Syndrome/diagnosis/genetics/*therapy
Wiskott-Aldrich Syndrome Protein/*genetics

Figure

• 

  Fig. 1 Sequence analysis showing genetic correction of the WASP gene in UPN 1. DNA sequences are shown that encompass a single point mutation (C to T) or a correction in exon 7 of the WASP gene. The asterisk denotes a C to T transversion or the T to C correction.

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