Identifying the genetic basis of variably protease-sensitive prionopathy

项目摘要 VPSPr是一种罕见的神经退行性疾病，临床表现为 路易体痴呆或额颞叶变性，但在神经病理学上与沉积物有关 感染性但对蛋白酶敏感的朊病毒蛋白（PrP）聚集体。VPSPr病例缺乏朊病毒突变 蛋白质基因（PRNP），但42%的病例有阳性家族史，符合遗传性疾病， 中度昏迷我们将应用全外显子组测序和深度靶向测序来查询 VPSPr的遗传基础VPSPr的遗传原因的鉴定将有助于朊病毒的鉴别诊断 疾病和阿尔茨海默氏症相关的痴呆症，验证新的基因组技术， 神经退行性疾病，并确定导致神经退行性疾病的新的细胞通路。

PROJECT SUMMARY First characterized one decade ago, VPSPr is a rare neurodegenerative disease that presents clinically as Lewy body dementia or frontotemporal lobar degeneration but has been neuropathologically linked to deposits of infectious but protease-sensitive prion protein (PrP) aggregates. VPSPr cases lack mutations in the prion protein gene (PRNP) but 42% of cases have a positive family history, consistent with a genetic disease of moderate penetrance. We will apply whole exome sequencing and deep targeted sequencing to query the genetic basis of VPSPr. Identification of a genetic cause of VPSPr will aid in the differential diagnosis of prion disease and Alzheimer’s-related dementias, validate new genomic technologies for understanding neurodegeneration, and identify new cellular pathways that lead to neurodegenerative disease.