title: CGG-repeat expansion in FMR1 is not associated with amyotrophic lateral sclerosis.
abstract: Recently, repeat expansions in several genes have been shown to cause or be associated with amyotrophic lateral sclerosis (ALS). It has been demonstrated that an intronic hexanucleotide repeat expansion in C9ORF72 is a major cause of both familial (approximately 40%) and sporadic (approximately 5%) ALS, as well as frontotemporal dementia (FTD). In addition, a CAG-repeat expansion in exon 1 of ATXN2, otherwise known to cause spinocerebellar ataxia type 2, has been identified as a major risk factor for sporadic ALS. Intermediate repeat expansions in the fragile X mental retardation 1 (FMR1) gene (55-200 repeats) are known to cause fragile X-associated premature ovarian insufficiency [(FX)POI; female carriers] or fragile X-associated tremor/ataxia syndrome (FXTAS; male carriers) by CGG-mediated RNA toxicity. The present investigation involves screening FMR1 repeat length in 742 sporadic ALS patients and 792 matched controls. Our conclusion is that FMR1 repeat expansions are not associated with ALS.
authors.affiliation: Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ewout J N
authors.initials: EJ
authors.lastname: Groen
authors.forename: Wouter
authors.initials: W
authors.lastname: van Rheenen
authors.forename: Max
authors.initials: M
authors.lastname: Koppers
authors.forename: Perry T C
authors.initials: PT
authors.lastname: van Doormaal
authors.forename: Lotte
authors.initials: L
authors.lastname: Vlam
authors.forename: Frank P
authors.initials: FP
authors.lastname: Diekstra
authors.forename: Dennis
authors.initials: D
authors.lastname: Dooijes
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Pasterkamp
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D012307:Risk Factors
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D005819:Genetic Markers; C497683:FMR1 protein, human