FTD-PSP is an Unusual Clinical Phenotype in A Frontotemporal Dementia Patient with A Novel Progranulin Mutation.
FTD-PSP is an Unusual Clinical Phenotype in A Frontotemporal Dementia Patient with A Novel Progranulin Mutation.
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DOI：
10.14336/ad.2021.0309
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发表时间：
2021-10
影响因子：
7.4
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Deng B;Zheng Z;Zheng J;Yang W;Huang Y;Luo Y;Jin D;Shen L;Jin K;Wang Q
前颗粒蛋白（GRN）突变是额颞叶痴呆（FTD）的主要原因；FTD的临床表型谱比以前报道的要广泛得多。中国FTD患者中GRN突变的频率和位置仍不确定。我们对一名最初出现FTD症状的散发性男性患者进行了cDNA测序。应用脑磁共振成像（MRI）和正电子发射计算机断层扫描/计算机断层扫描（PET/CT）进一步证实该患者的FTD诊断。通过细胞凋亡和存活试验验证GRN的功能。我们在该患者中发现了一种新的错义GRN突变（c.1498G>A, p.V500I），该患者最初表现为典型的行为变异型额颞叶痴呆（bvFTD）特征，但在发病5年后表现为进行性核上性麻痹（PSP）临床特征。此外，WT GRN蛋白在无血清培养基中表现出足够的营养刺激以维持SH-SY5Y细胞的存活，而GRN突变（c.1498G>A, p.V500I）可能会损害支持细胞存活的能力。本研究对遗传咨询和临床异质性具有重要意义。我们说明了这样一个事实，即在一名患者中呈现bvFTD和PSP特征的FTD可以被认为是GRN突变患者的特定表型。GRN p.V500I在体外诱导神经元变性；这一发现为该突变可能是FTD患者的一种新的致病突变提供了重要证据。
Progranulin (GRN) mutations are a major cause of frontotemporal dementia (FTD); the spectrum of clinical phenotypes of FTD is much more extensive than previously reported. The frequency and locations of GRN mutations in Chinese patients with FTD remain uncertain. We performed cDNA sequencing in one sporadic male patient who initially presented FTD symptoms. Brain magnetic resonance imaging (MRI) and positron emission computed tomography/computed tomography (PET/CT) were applied to further confirm the diagnosis of FTD from this patient. Cellular apoptosis and survival test were performed to identify the function of GRN. We identified one novel missense GRN mutation (c.1498G>A, p.V500I) in this patient, who initially presented typical behavioral-variant frontotemporal dementia (bvFTD) features but then presented progressive supranuclear palsy (PSP) clinical characteristics 5 years after onset. Besides, WT GRN protein showed an adequate trophic stimulus to preserve the survival of SH-SY5Y cells in the medium free of serum, while GRN mutation (c.1498G>A, p.V500I) may impair the ability of supporting cell survival. This study owns significant implications for genetic counseling and clinical heterogeneity. We illustrate the fact that FTD presenting features of bvFTD and PSP in one patient could be considered as a specific phenotype in patients with GRN mutations. GRN p.V500I led to the neuronal degeneration in vitro; this finding provides a significant evidence that this mutation may be a new causative mutation in patients with FTD.
影响因子：
5
作者：
Lashley T;Rohrer JD;Mahoney C;Gordon E;Beck J;Mead S;Warren J;Rossor M;Revesz T
通讯作者：
Revesz T