Screening for OPTN mutations in a cohort of British amyotrophic lateral sclerosis patients

Variants within the optineurin gene (OPTN) are recognized as causative mutations for primary open angle glaucoma. However, 4 different nonsynonymous and 3 different exonic deletion OPTN mutations have recently been identified in Japanese amyotrophic lateral sclerosis (ALS) patients. We sought to characterize OPTN genetic variation in a British cohort of ALS cases of Northern European origin. The coding portion of the gene (exons 4-16) was sequenced in a minimum of 75 familial and 120 sporadic ALS patients and an additional 300 sporadic cases in exons previously identified as harboring mutations in Northern European ALS patients. Ten variants were identified, 8 of which are present in single nucleotide polymorphism databases. Two novel synonymous changes were detected in exon 6 from 2 familial ALS cases. These are not predicted to alter splicing and are therefore unlikely to be pathogenic. We conclude that OPTN mutations associated with ALS are rare in British ALS patients.