Genetic and functional characters of GRN p.T487I mutation in Taiwanese patients with atypical parkinsonian disorders

Kuo Hsuan Chang, Guan Chiun Lee, Chin Chang Huang, Hung Chou Kuo, Chiung Mei Chen, Ya Chin Hsiao, Hsuan Chu Hsu, Ke Jen Hsu, Chih Hsin Lin, Chia Wen Chang, Guey Jen Lee-Chen, Yih Ru Wu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Mutations in the GRN (granulin precursor) are a frequent cause of frontotemporal dementia (FTD) and other atypical parkinsonian disorders. However, the frequency of GRN mutations in Asian patients with atypical parkinsonian disorders is still uncertain. Methods: We screened GRN mutations by sequencing cDNA from 98 patients with FTD or atypical parkinsonian disorders. The functional properties of the identified mutation were evaluated by overexpression in human embryonic kidney (HEK)-293 cells. Results: We identified a new missense (GRN p.T487I) mutation in a female patient with undefined atypical parkinsonism. The overexpression experiment further demonstrated that p.T487I mutation reduced the progranulin protein level and stability in HEK-293 cells. Conclusion: GRN p.T487I mutation, which decreases the stability of progranulin protein, could be a new causative mutation in patients with atypical parkinsonian disorders.

Original languageEnglish
Pages (from-to)61-66
Number of pages6
JournalParkinsonism and Related Disorders
Volume51
DOIs
Publication statusPublished - 2018 Jun

    Fingerprint

Keywords

  • GRN
  • Parkinsonism
  • Progranulin

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Chang, K. H., Lee, G. C., Huang, C. C., Kuo, H. C., Chen, C. M., Hsiao, Y. C., Hsu, H. C., Hsu, K. J., Lin, C. H., Chang, C. W., Lee-Chen, G. J., & Wu, Y. R. (2018). Genetic and functional characters of GRN p.T487I mutation in Taiwanese patients with atypical parkinsonian disorders. Parkinsonism and Related Disorders, 51, 61-66. https://doi.org/10.1016/j.parkreldis.2018.02.045