新型颗粒蛋白聚糖缺失与不同表型相关的临床和分子特征。
Clinical and Molecular Characterization of a Novel Progranulin Deletion Associated with Different Phenotypes.
机构信息
Center for Neurodegenerative Diseases (CEMAND); Department of Medicine, Surgery and Dentistry, Neuroscience Section, University of Salerno, Italy.
Institute of Biochemistry and Cell Biology (IBBC), CNR, Naples, Italy.
出版信息
J Alzheimers Dis. 2020;76(1):341-347. doi: 10.3233/JAD-200151.
BACKGROUND
Mutations in the GRN gene are causative for an autosomal dominant form of frontotemporal dementia.
OBJECTIVE/METHODS: The objective of the present study is to describe clinical and molecular features of three siblings harboring the GRN deletion NM_002087.3:c.295_308delTGCCCACGGGGCTT, p.(Cys99Profs*15) identified with next generation sequencing.
RESULTS
Our patients demonstrated heterogeneous clinical phenotypes, such as progressive supranuclear palsy-like in the proband and the behavioral variant of frontotemporal dementia in the two affected siblings. Progranulin haploinsufficiency was revealed by both gene expression and protein analyses.
CONCLUSION
The pathogenicity of the novel GRN deletion c.295_308del TGCCCACGGGGCTT is confirmed by both functional analysis and segregation in three affected siblings.
背景
GRN 基因突变可导致常染色体显性形式的额颞叶痴呆。
目的/方法：本研究的目的是描述携带 GRN 缺失 NM_002087.3:c.295_308delTGCCCACGGGGCTT，p.(Cys99Profs*15)的三个兄弟姐妹的临床和分子特征，该缺失是通过下一代测序发现的。
结果
我们的患者表现出异质性的临床表型，例如先证者表现为进行性核上性麻痹样，而两个受影响的兄弟姐妹则表现为额颞叶痴呆的行为变异型。基因表达和蛋白质分析显示颗粒蛋白前体基因单倍体不足。
结论
该 novel GRN deletion c.295_308del TGCCCACGGGGCTT 通过三个受影响的兄弟姐妹中的功能分析和分离得到证实。
Zotero 插件