title: Current insights into the C9orf72 repeat expansion diseases of the FTLD/ALS spectrum.
abstract: An expanded G4C2 hexanucleotide repeat in the proximal regulatory region of C9orf72 is a frequent cause of neurodegenerative diseases in the frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND) spectrum. Although primarily characterized by variably abundant pathological inclusions of TDP-43 protein, the lesion load was extended to TDP-43-negative, p62-positive neuronal and glial inclusions in extended regions of the central nervous system (CNS), particularly in cerebellum, where they may be characteristic of a C9orf72 repeat expansion. Disease mechanisms associated with repeat expansion disorders, including haploinsufficiency, RNA toxicity, and abnormal translation of expanded repeat sequences, are beginning to emerge. We review genetic, clinical, and pathological highlights and discuss current insights into the biology of this novel type of repeat expansion disease.
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Cruts
authors.forename: Ilse
authors.initials: I
authors.lastname: Gijselinck
authors.forename: Tim
authors.initials: T
authors.lastname: Van Langenhove
authors.forename: Julie
authors.initials: J
authors.lastname: van der Zee
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D000073885:C9orf72 Protein; D042622:DNA Repeat Expansion / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D057174:Frontotemporal Lobar Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D008957:Models, Genetic; D011506:Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins; D011506:Proteins
keywords: C9orf72; TDP43-proteinopathy; amyotrophic lateral sclerosis; frontotemporal lobar degeneration; neurodegeneration; repeat expansion diseases