Adult-Onset Neuronal Ceroid Lipofuscinosis With a Novel DNAJC5 Mutation Exhibits Aberrant Protein Palmitoylation

Qiang Huang; Yong-Fang Zhang; Lin-Jie Li; Eric B Dammer; Yong-Bo Hu; Xin-Yi Xie; Ran Tang; Jian-Ping Li; Jin-Tao Wang; Xiang-Qian Che; Gang Wang; Ru-Jing Ren

doi:10.3389/fnagi.2022.829573

Adult-Onset Neuronal Ceroid Lipofuscinosis With a Novel DNAJC5 Mutation Exhibits Aberrant Protein Palmitoylation

Front Aging Neurosci. 2022 Apr 8:14:829573. doi: 10.3389/fnagi.2022.829573. eCollection 2022.

Authors

Qiang Huang^{1

2

3}, Yong-Fang Zhang^{2

3}, Lin-Jie Li⁴, Eric B Dammer⁵, Yong-Bo Hu^{1

6}, Xin-Yi Xie¹, Ran Tang¹, Jian-Ping Li¹, Jin-Tao Wang¹, Xiang-Qian Che¹, Gang Wang¹, Ru-Jing Ren¹

Affiliations

¹ Department of Neurology, Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Shanghai Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ iHuman Institute, Shanghai Tech University, Shanghai, China.
⁵ Department of Biochemistry, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, United States.
⁶ Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

Neuronal ceroid lipofuscinosis (NCL) is composed of a group of inherited neurodegenerative diseases, with the hallmark of lipofuscin deposit (a mixture of lipids and proteins with metal materials) inside the lysosomal lumen, which typically emits auto-fluorescence. Adult-onset NCL (ANCL) has been reported to be associated with a mutation in the DNAJC5 gene, including L115R, L116Δ, and the recently identified C124_C133dup mutation. In this study, we reported a novel C128Y mutation in a young Chinese female with ANCL, and this novel mutation caused abnormal palmitoylation and triggered lipofuscin deposits.

Keywords: adult-onset neuronal ceroid lipofuscinosis; cognitive decline; cysteine string protein α; lysosome; neurodegenerative disease.