TY - JOUR
T1 - Novel optineurin mutations in sporadic amyotrophic lateral sclerosis patients
AU - van Blitterswijk, Marka
AU - van Vught, Paul W. J.
AU - van Es, Michael A.
AU - Schelhaas, Helenius J.
AU - van der Kooi, Anneke J.
AU - de Visser, Marianne
AU - Veldink, Jan H.
AU - van den Berg, Leonard H.
PY - 2012
Y1 - 2012
N2 - Optineurin (OPTN) mutations have been reported in a cohort of Japanese patients with familial (PALS) and sporadic (SALS.) amyotrophic lateral sclerosis. In Caucasian patients, OPTN mutations have been identified in PALS 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 PALS, 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. (C) 2012 Published by Elsevier Inc
AB - Optineurin (OPTN) mutations have been reported in a cohort of Japanese patients with familial (PALS) and sporadic (SALS.) amyotrophic lateral sclerosis. In Caucasian patients, OPTN mutations have been identified in PALS 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 PALS, 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. (C) 2012 Published by Elsevier Inc
U2 - https://doi.org/10.1016/j.neurobiolaging.2011.05.019
DO - https://doi.org/10.1016/j.neurobiolaging.2011.05.019
M3 - Article
C2 - 21802176
SN - 0197-4580
VL - 33
SP - 1016.e1-1016.e7
JO - Neurobiology of aging
JF - Neurobiology of aging
IS - 5
ER -