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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。A型和B型尼曼-匹克病（NPD）是由酸性鞘磷脂酶（ASM）缺乏引起的储存障碍。A型NPD是一种严重的神经性疾病，通常在三岁前死亡。相比之下，B型NPD患者很少或没有神经系统的影响，通常存活到青春期晚期或成年期。尽管这种疾病早在70多年前就被描述出来了，但没有治疗方法可以治疗受影响的患者，也没有可靠的生化测试来预测新诊断个体的表型结果。因此，本提案的具体目标是：1)表征B型疾病的自然历史和表型谱，为该疾病的酶替代疗法（ERT）的未来临床试验做准备；2)确定致病的ASM突变；3)确定基因型/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