NEUROFIBROMATOSIS SCREENING

神经纤维瘤病筛查

• 批准号: 7604963
• 负责人: DAVID K STEVENSON
• 金额: $ 2.63万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604963
• 关键词: Address; Area; Biological Process; Bone Diseases; Child health care; Clinical; Computer Retrieval of Information on Scientific Projects Database; Defect; Development; Developmental Bone Diseases; Dual-Energy X-Ray Absorptiometry; Dysplasia; Funding; General Population; Genotype; Grant; Hereditary Disease; Individual; Institution; Localized; Macrocephaly; Morbidity - disease rate; Mutation; NF1 gene; Natural History; Neurocutaneous Syndromes; Neurofibromatoses; Neurofibromatosis 1; Neurofibromatosis Type 1 Protein; Other Biochemical Pathway; Outcome; Pathogenesis; Patients; Peripheral; Phenotype; Pseudarthrosis; Reporting; Research; Research Personnel; Resources; Scallop; Screening procedure; Skeletal system; Source; Spinal; Tumor Suppressor Proteins; United States National Institutes of Health; Wing; X-Ray Computed Tomography; bone; bone healing; bone health; bone metabolism; clinical phenotype; crosslink; indexing; insight; long bone; rib bone structure; scoliosis; spine bone structure; urinary

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. Neurofibromatosis type 1 (NF1) is a common genetic disorder with good potential for insight into biological processes. It is classically characterized as a neurocutaneous disorder, but osseous and spinal abnormalities are clearly associated with NF1. Skeletal abnormalities associated with NF1 include long bone dysplasia (2-5%), sphenoid wing dysplasia (3-7%), and spinal abnormalities (10-33%). These complications are not well understood and rarely emphasized, even though as high as 38% have been reported to have osseous manifestations. The management of tibial pseudarthrosis and dystrophic scoliosis presents a significant challenge to practitioners. As yet, there is no easy explanation for the mesodermally derived osseous defects in NF1. Neurofibromin, the NF1 gene product, has tumor suppressor aspects through its interactions with ras, and may interact with other biochemical pathways involved in bone metabolism. Questions regarding pathogenesis, natural history, burden of morbidity, and clinical outcome remain unanswered. If generalized skeletal abnormalities exist in NF1 then some patients may be predisposed to develop localized defects. We theorize that there is a subtle primary disorder of bone in NF1 that predisposes NF1 individuals to the development of local, more severe osseous defects. Generalized osseous findings in NF1 include short stature and macrocephaly. Many of the localized osseous findings in NF1 (vertebral wedging and scalloping, rib-penciling, osteopenia and poor bone healing in long bone bowing with pseudarthrosis, localized overgrowth, and multiple cystic areas of bone in some patients) appear randomly, supporting this hypothesis. We hypothesize that there are generalized bone abnormalities with decreased bone health indexes in patients with NF1 compared to the general population. We also hypothesize that there is a phenotype-genotype correlation in NF1 patients with osseous defects. We will address these hypotheses with two corresponding specific aims. Specific aim #1: Describe the bone health of children with neurofibromatosis type 1 (NF1) using peripheral quantitative computerized tomography (pQCT), dual energy X-ray absorptiometry (DXA), and urinary pyridinium crosslinks. Specific aim #2: Describe the genotype-phenotype relationships of NF1 and osseous defects using mutation screening of the NF1 gene and clinical phenotyping.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 1 型神经纤维瘤病 (NF1) 是一种常见的遗传性疾病，具有深入了解生物过程的良好潜力。 它的典型特征是神经皮肤疾病，但骨和脊柱异常显然与 NF1 相关。 与 NF1 相关的骨骼异常包括长骨发育不良 (2-5%)、蝶骨翼发育不良 (3-7%) 和脊柱异常 (10-33%)。 尽管据报道高达 38% 的并发症有骨表现，但这些并发症尚未得到很好的理解，也很少受到重视。 胫骨假关节和营养不良性脊柱侧凸的治疗对从业者提出了重大挑战。 迄今为止，对于 NF1 中胚层衍生的骨缺损还没有简单的解释。 神经纤维蛋白（NF1 基因产物）通过与 ras 的相互作用具有肿瘤抑制作用，并且可能与参与骨代谢的其他生化途径相互作用。 有关发病机制、自然史、发病负担和临床结果的问题仍未得到解答。 如果 NF1 存在全身骨骼异常，那么一些患者可能容易出现局部缺陷。 我们推测 NF1 中存在一种微妙的原发性骨骼疾病，使 NF1 个体容易出现局部更严重的骨缺损。 NF1 的普遍骨质表现包括身材矮小和大头畸形。 NF1 中的许多局部骨质表现（椎体楔入和扇形、肋骨弯曲、骨质减少和长骨弯曲的骨愈合不良伴假关节、局部过度生长以及某些患者的多个骨囊性区域）随机出现，支持了这一假设。 我们假设 NF1 患者与一般人群相比存在普遍的骨异常，骨健康指数下降。 我们还假设患有骨缺损的 NF1 患者存在表型-基因型相关性。 我们将通过两个相应的具体目标来解决这些假设。 具体目标#1：使用外周定量计算机断层扫描 (pQCT)、双能 X 射线吸收测定法 (DXA) 和尿吡啶交联来描述 1 型神经纤维瘤病 (NF1) 儿童的骨骼健康状况。 具体目标#2：使用 NF1 基因突变筛查和临床表型分析来描述 NF1 和骨缺损的基因型-表型关系。