Novel optineurin mutations in sporadic amyotrophic lateral sclerosis patients

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• 作者：Marka van Blitterswijk^a ; Paul W.J. van Vught^a ; Michael A. van Es^a ; Helenius J. Schelhaas^b ; Anneke J. van der Kooi^c ; Marianne de Visser^c ; Jan H. Veldink^a ; ¹ ; Leonard H. van den Berg^a ; ¹ ; ^{L.H.vandenBerg@umcutrecht.nl}
• 关键词：Amyotrophic lateral sclerosis ; Motor neuron disease ; Familial ALS ; Genetics ; Optineurin ; Mutations
• 刊名：Neurobiology of Aging
• 出版年：2012
• 期刊代码：202_01974580
• 类别：med
• 出版时间：May, 2012
• 卷：33
• 期：5
• 页码：1016.e1-1016.e7
• 文件大小：1135 K

摘要

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.