학술논문
Extensive transcriptomic study emphasizes importance of vesicular transport in C9orf72 expansion carriers
Document Type
article
Author
Dennis W. Dickson; Matthew C. Baker; Jazmyne L. Jackson; Mariely DeJesus-Hernandez; NiCole A. Finch; Shulan Tian; Michael G. Heckman; Cyril Pottier; Tania F. Gendron; Melissa E. Murray; Yingxue Ren; Joseph S. Reddy; Neill R. Graff-Radford; Bradley F. Boeve; Ronald C. Petersen; David S. Knopman; Keith A. Josephs; Leonard Petrucelli; Björn Oskarsson; John W. Sheppard; Yan W. Asmann; Rosa Rademakers; Marka van Blitterswijk
Source
Acta Neuropathologica Communications, Vol 7, Iss 1, Pp 1-21 (2019)
Subject
Language
English
ISSN
2051-5960
Abstract
Abstract The majority of the clinico-pathological variability observed in patients harboring a repeat expansion in the C9orf72-SMCR8 complex subunit (C9orf72) remains unexplained. This expansion, which represents the most common genetic cause of frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND), results in a loss of C9orf72 expression and the generation of RNA foci and dipeptide repeat (DPR) proteins. The C9orf72 protein itself plays a role in vesicular transport, serving as a guanine nucleotide exchange factor that regulates GTPases. To further elucidate the mechanisms underlying C9orf72-related diseases and to identify potential disease modifiers, we performed an extensive RNA sequencing study. We included individuals for whom frontal cortex tissue was available: FTLD and FTLD/MND patients with (n = 34) or without (n = 44) an expanded C9orf72 repeat as well as control subjects (n = 24). In total, 6706 genes were differentially expressed between these groups (false discovery rate [FDR]