CANCER AND MORTALITY IN NEUROFIBROMATOSIS BY GENOTYPE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。这项工作的目的是评估NF1基因在个人和他们的家庭成员与神经纤维瘤病（NF1）或怀疑有NF1。评估NF1基因的突变是一个更大的项目的一部分，该项目通过基因型研究NF1的癌症和死亡率。每位患者将在俄克拉荷马州儿童医院或其他地方接受临床评估。在访问期间，患者将接受有关NF1和基因检测的风险和益处的咨询。这项研究将帮助我们将NF1基因中的特定突变与特定表型相关联。这些结果可能有助于医疗保健提供者确定NF1某些临床特征的风险，从而改善有关NF1患者的心理社会因素，预后和其他问题的教育和咨询。基因型-表型相关性也有助于引入新的治疗和干预措施，以及遗传筛查在预测疾病和NF1患者子女结局方面的有效性。NF1基因检测的改进可能有助于排除或排除NF1的疑似诊断。我们假设NF1基因内没有突变与特定终点相关，如早期死亡，特定癌症或任何其他医疗事件，事实上，这些事件在家庭内没有显着的聚集性。预期的结果是，至少有一个突变，突变区域或突变类别似乎与某个终点相关，例如那些具有明显过量癌症的NF1家族。部分支持这项基因检测的NIH资助父母的工作有三个具体目标。具体目标1-确定个人及其家庭成员中NF 1基因的特定突变。具体目标2-探索可能的NF 1突变特异性协会与某些表型。具体目标3-检验NF 1基因检测的临床有效性。在对研究志愿者进行临床评价时，我们通常会构建家谱，获取病史，并针对NF 1的诊断标准进行有针对性的体格检查。在患者（或父母）同意的情况下，我们将要求提供血液样本，通过蛋白质截短试验、单链构象多态性凝胶、自动荧光测序、RT-PCR或其他方法检测NF 1突变。将按NF 1基因型比较特定表型的发生率。口腔拭子可能是DNA的替代来源。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this work is to assess the NF1 gene in individuals and their family members with neurofibromatosis (NF1) or suspected of having NF1. Assessing the mutations in NF1 genes is part of a larger project on the study of cancer and mortality in NF1 by genotype. Each patient will have a clinical evaluation at Children's Hospital of Oklahoma or elsewhere. During the visit the patients will receive counseling about NF1 and the risk and benefits of gene testing. This study will help us correlate specific mutations in the NF1 gene with specific phenotypes. The results may help the health care providers determine the risks of developing certain clinical features of NF1, which can lead to improved education and counseling concerning psychosocial factors, prognostic and other concerns of NF1 patients. A genotype-phenotype correlation could also help to introduce new therapies and interventions, and the effectiveness of genetic screening in predicting the disease and the outcome in the children of people with NF1. Improvements of a gene test for NF1 may be useful for ruling in or out a suspected diagnosis of NF1. We hypothesize that no mutation within the NF1 gene is associated with a specific endpoint, such as early death, a specific cancer, or any other medical event and that such events, in fact, show no significant clustering within families. The expected result is that at least one mutation, region of mutation, or class of mutation will appear to be associated with a certain endpoint, such as those families with NF1 that have an apparent excess of cancer. The work of the NIH grant parent that partly supports this gene assay has three specific aims. Specific Aim 1 - To determine the specific mutation within the NF1 gene in individuals and their family members. Specific Aim 2 - To explore possible NF1 mutation-specific associations with certain phenotypes. Specific Aim 3 - To assay the clinical validity of NF1 gene testing. During the clinical evaluation of study volunteers, we will usually construct a family tree, obtain medical history, and conduct targeted physical examination for diagnostic criteria of NF1. With the patient's (or parents') consent, we will request a blood sample for testing for NF1 mutations by a protein truncation assay, single-stranded conformation polymorphism gels, automatic fluorescent sequencing, RT-PCR, or other methods. The incidence of specific phenotypes will be compared by NF1 genotype. Buccal swabs may be an alternative source of DNA.