Narrowing the candidate interval of the Wiskott-Aldrich syndrome by a proximal recombination event detected by linkage analysis and X inactivation study
- Univ. of Munich (Germany); and others
The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency combined with thrombocytopenia in which the molecular defect is still unknown. Initial linkage data placed the WAS gene between TIMP and the marker DXS255 in Xp11.23 to Xp11.22. As no recombination was detected between the disease locus closely linked to DXS255 and the marker loci OATL1, SYP and TFE3, the position of WAS relative to these polymorphic loci could not yet be determined. In this study, further segregation analysis has been performed using additional (CA)n repeats DXS1367, DXS6616 and DXS1126. While DXS1367 and DXS6616 could be mapped adjacent to OATL1, location of DXS1126 between OATL1 and TFE3 is demonstrated. In a WAS pedigree of three generations (4 affected males, 10 obligate female carriers, 7 non-carriers) we observed a recombination event between the disease and the locus TIMP, DXSS1367, and DXS6616 in a patient manifesting WAS and the daughter of his female cousin. The carrier status of the female relative was confirmed or excluded by X inactivation analysis. No recombination was detected by the marker DXS6616 containing the zinc finger genes ZNF21 and ZNF81 as a candidate region of the Wiskott-Aldrich syndrome and narrows the boundaries to an interval bracketed by DXS6616 and DXS255. In addition, the current results identify the DXS1367 probe as a useful diagnostic marker for indirect genotype analysis of the Wiskott-Aldrich syndrome.
- OSTI ID:
- 134115
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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