title: Novel optineurin mutations in sporadic amyotrophic lateral sclerosis patients.
abstract: Optineurin (OPTN) mutations have been reported in a cohort of Japanese patients with familial (FALS) and sporadic (SALS) amyotrophic lateral sclerosis. In Caucasian patients, OPTN mutations have been identified in FALS patients, but were not detected in a cohort of 95 SALS patients. Moreover, single nucleotide polymorphisms (SNPs) in OPTN that could raise amyotrophic lateral sclerosis (ALS) susceptibility have not been investigated. Therefore, we screened a large Dutch cohort of 1191 patients with SALS, 94 patients with FALS, and 1415 control subjects for mutations and SNPs in OPTN. We identified 1 novel nonsense mutation (Q165X) and 1 unreported missense mutation (Q454E) in individual SALS patients. These patients demonstrated rapid disease progression with an average survival of 24.5 months. No heterozygous or homozygous OPTN mutations were identified in our cohort of FALS patients. SNP analysis did not reveal significant differences between ALS patients and control subjects. Therefore, variations in OPTN appear to be a rare cause of rapidly progressive SALS in the Netherlands.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Marka
authors.initials: M
authors.lastname: van Blitterswijk
authors.forename: Paul W J
authors.initials: PW
authors.lastname: van Vught
authors.forename: Michael A
authors.initials: MA
authors.lastname: van Es
authors.forename: Helenius J
authors.initials: HJ
authors.lastname: Schelhaas
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D018389:Codon, Nonsense / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D035582:Transcription Factor TFIIIA / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA