FTD-PSP is an unusual clinical phenotype in a frontotemporal dementia patient with a novel progranulin mutation

Bin Deng, Zhe Zheng, Jialing Zheng, Wanlin Yang, Yu Huang, Yuqi Luo, Dana Jin, Lu Shen, Kunlin Jin, Qing Wang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1741-1752
Number of pages12
JournalAging and Disease
Volume12
Issue number7
DOIs
StatePublished - 1 Oct 2021

Keywords

  • Frontotemporal dementia
  • Mutation
  • Parkinson Syndrome
  • Progranulin
  • Progressive supranuclear palsy

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