NAIL PATELLA SYNDROME

指甲髌骨综合症

• 批准号: 7604591
• 负责人: JULIE E HOOVER-FONG
• 金额: $ 0.02万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604591
• 关键词: Affect; Animal Model; Clinical Data; Cohort Studies; Computer Retrieval of Information on Scientific Projects Database; Condition; Disease; Dysplasia; Early Diagnosis; Elbow; Eye; Funding; Genes; Glaucoma; Grant; Horns; Human; Individual; Institution; Intervention; Joint Dislocation; Kidney; Kidney Diseases; Kidney Failure; Knee bone; Lead; Limb structure; Molecular; Muscle; Mutation; Nail plate; Nail-Patella Syndrome; Organism; Patients; Phenotype; Regulation; Research; Research Personnel; Resources; Risk; Skeletal system; Source; Transact; United States National Institutes of Health; glomerular basement membrane; loss of function mutation; outcome forecast; transcription factor

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. Nail Patella Syndrome (NPS) is a pleiotropic autosomal dominant condition affecting the nails, skeletal system, kidneys and eyes. Skeletal features include absent or hypoplastic patellae, patella dislocations, elbow abnormalities, talipes and iliac horns. Kidney involvement may lead to renal failure and there is also a risk of glaucoma. Heterozygous loss of function mutations in the gene encoding the transcription factor LMX1B cause NPS in humans. Evidence from animal models suggest that loss of LMX1B function affects the dorso-ventral polarity of the developing limb, resulting in nail dysplasia, patellar hypoplasia and the aberrant muscle insertions observed among NPS patients. Because LMX1B is a transcription factor, some NPS disease manifestations are also due to abnormal downstream regulation of other transacting genes; this is evidenced by LMX1B's influence on COL4A4 expression in glomerular basement membrane. As progress is made to understand LMX1B's function at a molecular and cellular level, it is imperative that affected individuals are accurately phenotyped in order to understand the manifestations of LMX1B mutations at an organism level. This will allow earlier detection, intervention and, possibly treatment and prognosis of the disease components of NPS. Provisions to collect longitudinal clinical data from this NPS study cohort will also provide information about the progression of kidney disease that can then be applied to all NPS patients.

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。子项目和 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。 指甲髌骨综合征 (NPS) 是一种多效性常染色体显性遗传疾病，影响指甲、骨骼系统、肾脏和眼睛。 骨骼特征包括髌骨缺失或发育不良、髌骨脱位、肘部异常、足足和髂角。 肾脏受累可能会导致肾功能衰竭，并且还有患青光眼的风险。 编码转录因子 LMX1B 的基因中的杂合性功能缺失突变会导致人类 NPS。来自动物模型的证据表明，LMX1B 功能的丧失会影响发育中肢体的背腹极性，导致 NPS 患者中观察到的指甲发育不良、髌骨发育不全和肌肉插入异常。 由于LMX1B是一种转录因子，一些NPS疾病的表现也是由于其他转录基因的下游调控异常所致； LMX1B 对肾小球基底膜中 COL4A4 表达的影响证明了这一点。 随着在分子和细胞水平上了解 LMX1B 功能的进展，必须对受影响的个体进行准确的表型分析，以便在生物体水平上了解 LMX1B 突变的表现。 这将使 NPS 疾病的早期检测、干预以及可能的治疗和预后成为可能。 从 NPS 研究队列中收集纵向临床数据的规定还将提供有关肾脏疾病进展的信息，然后将其应用于所有 NPS 患者。