title: The Genetics ofC9orf72Expansions.
abstract: Repeat expansions in the promoter region ofC9orf72are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and related disorders of the ALS/frontotemporal lobar degeneration (FTLD) spectrum. Remarkable clinical heterogeneity among patients with a repeat expansion has been observed, and genetic anticipation over different generations has been suggested. Genetic factors modifying the clinical phenotype have been proposed, including genetic variation in other known disease genes, the genomic context of theC9orf72repeat, and expanded repeat size, which has been estimated between 45 and several thousand units. The role of variability in normal and expanded repeat sizes for disease risk and clinical phenotype is under debate. Different pathogenic mechanisms have been proposed, including loss of function, RNA toxicity, and dipeptide repeat (DPR) protein toxicity resulting from abnormal translation of the expanded repeat, but the major mechanism is yet unclear.
authors.affiliation: Department of Molecular Genetics, VIB, University of Antwerp, 2610 Antwerp, Belgium.|Institute Born-Bunge, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Gijselinck
authors.affiliation: Department of Molecular Genetics, VIB, University of Antwerp, 2610 Antwerp, Belgium.|Institute Born-Bunge, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Cruts
authors.affiliation: Department of Molecular Genetics, VIB, University of Antwerp, 2610 Antwerp, Belgium.|Institute Born-Bunge, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D000073885:C9orf72 Protein / Q000235:genetics* / Q000378:metabolism; D042622:DNA Repeat Expansion; D057180:Frontotemporal Dementia / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D010641:Phenotype; D020033:Protein Isoforms / Q000378:metabolism; D012307:Risk Factors
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D020033:Protein Isoforms