Molecular Mechanisms of Familial Hemophagocytic Lymphohistiocytosis

2009年，我们为我们的研究奠定了基础，首先从我们的机构审查委员会获得了一项新的研究方案的批准，该方案允许我们收集移植的FHLH患者的皮肤活检。这一方案不仅允许我们分离生殖系DNA(从移植的血细胞之外)，还允许我们建立产生可诱导的多能干细胞(IPS)所需的成纤维细胞培养。我们已经开始从正常的健康志愿者身上培养成纤维细胞，作为在我们的患者身上做同样的事情的前奏。 由于我们的候选基因研究集中在先前定位的9p21基因座上，到目前为止在几个FHLH患者样本中尚未发现，我们计划进行一项新的基因连锁研究来证实和扩大这一发现。在这项研究中，我们收集了大约一半的DNA样本，这些样本来自没有已知突变的多基因家庭的父母和受影响的后代。我们的研究将被用来检测两个基因座。

In 2009, we laid the groundwork for our studies, starting with obtaining approval from our institutional review board for a new research protocol that allows us to collect skin biopsies from transplanted FHLH patients. This protocol permits us not only to isolate germline DNA (from other than the transplanted blood cells), but also to establish fibroblast cultures needed for generating inducible pluripotent stem cells (iPS) cells. We have started growing fibroblast cultures from normal healthy volunteers as a prelude to doing the same in our patients. Because our candidate gene studies, focusing on the previously mapped 9p21 locus, have so far been unrevealing in several FHLH patient samples, we are planning a new gene linkage study to confirm and extend this finding. For this study, we have collected approximately half of the DNA samples from the parents and affected offspring of multiplex families that have no known mutations. Our study will be powered to detect two loci.