NIEMANN-PICK DISEASE: GENOTYPE/PHENOTYPE ANALYSES AND MOLECULAR BASED THERAPY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。A型和B型尼曼-皮克病(NPD)是由于酸性鞘磷脂酶(ASM)缺乏引起的贮藏性疾病。A型NPD是一种严重的神经性疾病，统一导致三岁前死亡。相比之下，B型NPD患者的神经系统病变很少或根本没有，通常会存活到青春期晚期或成年。尽管这种疾病在70多年前就已被描述，但目前还没有针对受影响患者的治疗方法，也没有开发出可靠的生化测试来预测新诊断个体的表型结果。因此，这项建议的具体目的是：1)表征B型疾病表型的自然病史和谱系，以期将来进行酶替代疗法(ERT)治疗这种疾病的临床试验；2)识别引起ASM突变，以及3)识别基因/表型相关性

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. Types A and B Niemann-Pick disease (NPD) are storage disorders resulting from the deficiency of acid sphingomyelinase (ASM). Type A NPD is a severe neuronopathic disorder which uniformly leads to death by three years of age. In contrast, patients with Type B NPD have little or no neurologic involvement and often survive into late adolescence or adulthood. Despite the fact that this disorder was described over seventy years ago, no treatment is available for affected patients and no reliable biochemical tests have been developed to predict the phenotypic outcome of newly diagnosed individuals. Thus, the specific aims of this proposal are to: 1) characterize the natural history and spectrum of the phenotype in Type B disease in anticipation of a future clinical trial of enzyme replacement therapy (ERT) for this disorder, 2) identify causative ASM mutations, and 3) identify genotype/phenotype correlations