SALIVA AS DIAGNOSTIC INDICATOR IN PRADER WILLI SYNDROME

唾液作为普威利综合征的诊断指标

• 批准号: 2132835
• 负责人: P Suzanne Hart
• 金额: $ 4.14万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-15 至 1996-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2132835
• 关键词: Prader Willi syndrome; SDS polyacrylamide gel electrophoresis; adolescence (12-20); atomic absorption spectrometry; body fluid viscosity; calcium; child (0-11); chlorine; chromosome deletion; diagnostic tests; early diagnosis; electrodes; family genetics; fluid flow; fluorine; genetic disorder; genetic markers; human subject; in situ hybridization; inborn metabolism disorder diagnosis; phosphorus; saliva; salivation; secretory protein; sodium

The long term objective of these research efforts is to develop a diagnostic test for Prader-Willi syndrome (PWS) based on saliva. PWS is a genetic disorder characterized by psychomotor and growth retardation, infantile hypotonia, characteristic facies, small hands and feet, and early onset of childhood hyperphagia with consequent obesity. Abnormal saliva has been a consistent finding in these individuals. An interstitial deletion of bands q11.2-q13 of the paternally derived chromosome 15 has been found in 70% of PWS patients. The majority of non- deletion PWS patients exhibit material disomy for chromosome 15, further demonstrating that loss of paternal alleles is responsible for the phenotype of PWS. The goal of these proposed studies is to determine what is abnormal about the saliva in these patients and to evaluate saliva's usefulness as a diagnostic sign of PWS. The Specific Aims of this proposal are l) To perform compositional studies on saliva from individuals with PWS and 2) To relate the underlying genetic defect in PWS patients to the salivary composition. Specific Aim l will be accomplished by the measurement of the concentrations of fluoride and chloride by ion specific electrode, of calcium and sodium by atomic absorption, and of phosphorus and total protein by spectrophotometric determination. The protein composition will be assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. If specific alterations of salivary components, such as calcium and phosphate concentrations, are found in the PWS individuals, these alterations could be used as a diagnostic test for early identification of PWS. This may be particularly valuable for females and African Americans who are at risk for remaining undiagnosed. It may also provide data regarding the mechanism of decreased salivary flow in these patients. Specific Aim 2 will be accomplished by a combination of cytogenetic (high resolution banding and fluorescence in situ hybridization) and molecular (methylation studies and the PCR-based CA dinucleotide repeat assay) techniques in order to determine the underlying genetic defect (deletion, uniparental disomy, or apparently normal constitution) in these patients. The comparison of the genetic defects will indicate alterations in salivary composition can be used to aid in the diagnosis of all subtypes of PWS. The understanding of altered salivary secretion in these individuals will lead to a better comprehension of normal saliva secretion and of secretion in general.

这些研究工作的长期目标是开发一种 基于唾液的普瑞德威利综合征 (PWS) 诊断测试。 PWS 是一种以精神运动和生长为特征的遗传性疾病 发育迟缓、婴儿肌张力低下、特征性面容、小手和 脚，以及儿童期早期出现的食欲过盛以及随之而来的肥胖。 这些人的唾液异常是一致的发现。一个 父系来源的带 q11.2-q13 的间隙缺失 70% 的 PWS 患者中发现了 15 号染色体。大多数非 缺失 PWS 患者表现出 15 号染色体物质二体性，进一步 证明父系等位基因的缺失是造成 PWS的表型。这些拟议研究的目标是确定什么 这些患者的唾液异常并评估唾液的 作为 PWS 的诊断标志的有用性。 该提案的具体目标是 l) 进行成分研究 2) 联系 PWS 患者的唾液 PWS患者的唾液成分存在遗传缺陷。 具体目标将通过测量来实现 通过离子特定电极测量氟化物和氯化物的浓度， 原子吸收法测定钙和钠，以及磷和总磷 分光光度法测定蛋白质。蛋白质成分将 通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳进行评估。 如果唾液成分发生特定改变，例如钙和 在 PWS 个体中发现了磷酸盐浓度，这些 改变可以用作早期识别的诊断测试 公共服务系统。这对于女性和非裔美国人来说可能特别有价值 那些有未被诊断的风险的人。它还可以提供数据 关于这些患者唾液流量减少的机制。 具体目标 2 将通过细胞遗传学（高 分辨率条带和荧光原位杂交）和分子 （甲基化研究和基于 PCR 的 CA 二核苷酸重复测定） 技术以确定潜在的遗传缺陷（缺失， 这些患者的单亲二体性，或表面上正常的体质）。 遗传缺陷的比较将表明 唾液成分可用于帮助诊断所有亚型 的 PWS。 了解这些个体唾液分泌的改变将 更好地理解正常唾液分泌和分泌物 一般来说。