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

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.

• Authors: 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
• Journal: Parkinsonism & related disorders (Parkinsonism Relat Disord) Vol. 51 Pg. 61-66 (06 2018) ISSN: 1873-5126 [Electronic] England
• PMID: 29530724 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• GRN protein, human
• Progranulins

Topics

• Aged
• Female
• Frontotemporal Dementia (genetics)
• HEK293 Cells
• Humans
• Male
• Middle Aged
• Mutation, Missense
• Parkinsonian Disorders (genetics)
• Progranulins (genetics)
• Taiwan