A 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 rece...

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Bibliographic Details
Published in:	Neurobiology of aging Vol. 33; no. 1; pp. 208.e1 - 208.e5
Main Authors:	Tümer, Zeynep, Bertelsen, Birgitte, Gredal, Ole, Magyari, Melinda, Nielsen, Karen Cecilie, LuCamp, Grønskov, Karen, Brøndum-Nielsen, Karen
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 2012
Subjects:	Adult Aged Aged, 80 and over Aging ALS Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - genetics Child Codon, Nonsense Denmark Exons Genetic Association Studies Glaucoma Glaucoma, Open-Angle - genetics Heterozygote Humans Internal Medicine Male Nervous system Neurodegenerative diseases Neurology Nonsense mutation Optineurin OPTN Superoxide dismutase Transcription Factor TFIIIA - genetics Denmark Glaucoma ALS Amyotrophic lateral sclerosis Optineurin OPTN
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Summary:	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.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0197-4580 1558-1497
DOI:	10.1016/j.neurobiolaging.2011.07.001