부산대학교 도서관

Mutations in the optineurin gene (OPTN) have been identified in a small proportion (<1%) of sporadic and familial ALS cases, and the exact role of optineurin in the pathogenesis of ALS remains unclear. To further examine the role ofOPTNin ALS, we sought to identify novel ALS variants inOPTNand examine their potential for pathogenicity in vitro. Whole exome sequence data from 74 familial ALS cases were analysed for the presence of novelOPTNmutations. Pathogenicity was assessed by analysing effects on Golgi fragmentation, endoplasmic reticulum (ER) stress-linked CHOP activation, and cellular localization of optineurin in motor neuron-like NSC-34 cells expressing mutant optineurin. We identified a novel heterozygous missense mutation inOPTN(c.883G > T, p.Val295Phe) in a single familial ALS case. This mutation induced recognized cellular features of ALS pathogenesis including Golgi fragmentation and ER stress in NSC-34 cells. In conclusion, the identification of a novelOPTNmutation in an Australian ALS family, and its capacity to induce ALS-like pathological features in vitro, further strengthens evidence for the role of optineurin in the pathogenesis of ALS. [ABSTRACT FROM AUTHOR]