NAIL PATELLA SYNDROME

指甲髌骨综合症

• 批准号: 7378866
• 负责人: JULIE E HOOVER-FONG
• 金额: $ 0.26万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378866
• 关键词: NAIL; PATELLA; SYNDROME

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来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。指甲-髌骨综合征（Nail Patella Syndrome，简称NPH）是一种多效常染色体显性遗传疾病，可累及指甲、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、肘关节异常、畸形足和髂角。肾脏受累可能导致肾衰竭，也有青光眼的风险。编码转录因子LMX 1B的基因中的杂合性功能丧失突变导致人类的染色体畸变。来自动物模型的证据表明，LMX 1B功能的丧失会影响发育肢体的背腹极性，导致指甲发育不良、髌骨发育不全和在骨关节炎患者中观察到的异常肌肉插入。由于LMX 1B是一种转录因子，一些肾小球疾病的表现也是由于其他反式作用基因的异常下游调控;这是由LMX 1B对肾小球基底膜中COL 4A 4表达的影响所证明的。随着在分子和细胞水平上了解LMX 1B功能的进展，必须对受影响的个体进行准确的表型分析，以了解LMX 1B突变在生物体水平上的表现。这将使早期发现，干预，并可能治疗和预后的疾病组成部分的疟疾。从这项研究队列中收集纵向临床数据的规定也将提供有关肾脏疾病进展的信息，然后可以应用于所有肾脏疾病患者。