Novel heterozygous nonsense mutation of the OPTN gene segregating in a Danish family with ALS

TY - JOUR

T1 - Novel heterozygous nonsense mutation of the OPTN gene segregating in a Danish family with ALS

AU - Tümer, Zeynep

AU - Bertelsen, Birgitte

AU - Gredal, Ole

AU - Magyari, Melinda

AU - Nielsen, Karen Cecilie

AU - Lucamp, null

AU - Grønskov, Karen

AU - Brøndum-Nielsen, Karen

N1 - Copyright © 2012 Elsevier Inc. All rights reserved.

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Amyotrophic Lateral Sclerosis

KW - Child

KW - Codon, Nonsense

KW - Denmark

KW - Genetic Association Studies

KW - Glaucoma, Open-Angle

KW - Heterozygote

KW - Humans

KW - Male

KW - Transcription Factor TFIIIA

U2 - 10.1016/j.neurobiolaging.2011.07.001

DO - 10.1016/j.neurobiolaging.2011.07.001

M3 - Journal article

C2 - 21852022

SN - 0197-4580

VL - 33

SP - 208.e1-5

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 1

ER -