The primary hypothesis of this proposal is that current molecular genetic testing for DiGeorge Anomaly (DGA) will predict which children with complex congenital heart disease (CCHD) are likely to have immunological and neurodevelopmental disorders. We propose that 1) an increased number and percentage of peripheral blood T cells in children with DiGeorge Anomaly express the gamma/phi T cell receptor instead of the classical TCRalpha beta due to defective thymic development and associated abnormal T-cell ontogeny. Furthermore, we propose that the TCR gene rearrangements are restricted in variability because most peripheral T cells in DGA originate extra-thymically from relatively few lymphocyte precursors. Specific molecular defects resulting from a hemizygous microdeletion in the human chromosome region 22q11.2 will be evident in thymic tissue from patients with the DGA. Neurodevelopmental testing will reflect the degree of developmental delay and predisposition for learning disabilities sometimes seen in older patients with DGA.
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