Mutation Analysis Of Selected Lymphoid Immune Disorders

该项目是为更好地描述和了解免疫缺陷而开展的一系列长期合作研究的延伸。目前正在利用荧光探针进行直接基因测序，对涉及共同γ链（X-SCID）和Fas （ALPS）基因的突变进行评估。这些研究继续在这两种疾病中确定了许多新的突变，这些数据已被输入NIH NHGRI网站，以支持这两种疾病。对编码Fas的基因（TNFRSF6）进行了广泛的评估，使用来自高加索人和非裔美国人的对照DNA样本来确定该基因中单核苷酸多态性的存在和频率。本研究的数据证实了9个snp，并在评估的对照DNA样本中发现了两个新的snp。目前正在评价和准备发表这些结果。此外，针对编码cd40l和NEMO基因的高IgM综合征患者的突变分析，在免疫缺陷程度和外胚层发育不良的存在与否的水平上，提供了与NEMO突变相关的临床表型变异性的见解。

This project represents an extension of a long-standing series of collaborative studies performed to better characterize and understand immune deficiency. Mutations involving the genes for the common gamma chain (X-SCID) and Fas (ALPS) are being evaluated using direct gene sequencing with fluorescent probes. These studies have continued to identify a number of new mutations in both diseases and these data have been entered into the NIH NHGRI web site supporting each of these two disorders. An extensive evaluation of the gene encoding Fas (TNFRSF6) has been undertaken using control DNA samples from Caucasian and African American control subjects to determine the presence and frequency of single nucleotide polymorphisms in this gene. The data from this study has confirmed 9 SNPs and identified two new SNPs among the control DNA samples evaluated. The results are currently being evaluated and prepared for publication. In addition, mutation analysis of patients with hyper IgM syndrome directed at the genes encoding CD40 L and NEMO has provided provided insight into the variability of the clinical phenotype associated with mutations in NEMO at the level of the degree of immunodeficiency and the presence or absence of ectodermal dysplasia.