title: Novel heterozygous nonsense mutation of the OPTN gene segregating in a Danish family with ALS.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. About 10% of ALS cases are familial (FALS) and the genetic defect is known only in approximately 20%-30% of these cases. The most common genetic cause of ALS is SOD1 (superoxide dismutase 1) mutation. Very recently, mutations of the optineurin gene (OPTN), which is involved in open-angle glaucoma, were identified in 3 Japanese patients/families with ALS, and subsequently in a few FALS patients of European descent. We found a heterozygous nonsense mutation (c.493C>T, p.Gln165X, exon 6) in the OPTN gene in a Danish patient with ALS, and the mutation segregated from his affected father. The p.Gln165X mutation could not be detected in 1070 healthy Danish controls, in 1000 Danish individuals with metabolic phenotypes or in 64 sporadic ALS (SALS) cases. The p.Gln165X mutation described in this study is the first mutation reported in a Danish family and is likely involved in disease pathogenesis. Until now, only few OPTN mutations have been associated with ALS. As the underlying genetic defect is known only in approximately 20%-30% of FALS families, further screening of these cases is necessary for establishing the contribution of OPTN mutations in disease pathogenesis.
authors.affiliation: Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark. zet@kennedy.dk
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tümer
authors.forename: Birgitte
authors.initials: B
authors.lastname: Bertelsen
authors.forename: Ole
authors.initials: O
authors.lastname: Gredal
authors.forename: Melinda
authors.initials: M
authors.lastname: Magyari
authors.forename: Karen Cecilie
authors.initials: KC
authors.lastname: Nielsen
authors.lastname: Lucamp
authors.forename: Karen
authors.initials: K
authors.lastname: Grønskov
authors.forename: Karen
authors.initials: K
authors.lastname: Brøndum-Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D018389:Codon, Nonsense; D003718:Denmark; D056726:Genetic Association Studies; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; 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