T CELL RECEPTOR GAMMA DELTA EXPRESSION IN CHILDREN WITH DIGEORGE ANOMALY

该提案的主要假设是，当前对迪乔治异常（DGA）的分子遗传学检测将预测哪些患有复杂先天性心脏病（CCHD）的儿童可能患有免疫和神经发育障碍。我们提出：1) 由于胸腺发育缺陷和相关的 T 细胞个体发育缺陷，DiGeorge 异常儿童的外周血 T 细胞数量和百分比增加，表达 gamma/phi T 细胞受体而不是经典的 TCRalpha beta。此外，我们认为 TCR 基因重排的变异性受到限制，因为 DGA 中的大多数外周 T 细胞源自胸腺外，来自相对较少的淋巴细胞前体。 人类染色体 22q11.2 区域半合子微缺失导致的特定分子缺陷在 DGA 患者的胸腺组织中会很明显。神经发育测试将反映老年 DGA 患者有时出现的发育迟缓程度和学习障碍倾向。

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.