A specific gene-splicing alteration in the SNRNP70 gene as a hallmark of an ALS subtype.

Amyotrophic lateral sclerosis (ALS) has been considered as one of the progressive neurodegenerative diseases. Numerous genetic factors in divergent molecular pathways have been identified as causative factors of ALS. However, the underlying molecular mechanism that causes this disease remains undetermined; as a result, this has driven the search to find consensus disease-specific hallmarks. In this study, we focused on the alteration of the ratio of two specific gene-splicing events in the SNRNP70 gene from RNA-seq data derived from patients with ALS and control subjects. The splicing profile was significantly and specifically changed in one previously identified ALS subtype. Conversely, the gene expression profile of other ALS cases containing a splicing alteration in the SNRNP70 gene was similar to that of the subtype, whereas ALS cases without this change have exhibited less similarity. These results indicate that this splicing event in the SNRNP70 gene could represent a novel and broadly applicable molecular hallmark of a subtype of ALS.