FIGURE 5.

Loss of TDP‐43 splicing activity in the presence of the Y374X‐TDP‐43 mutation. (A and B) Semi‐quantitative PCR revealed no evidence of abnormal POLDIP3/SKAR gene splicing in fibroblasts (A) from Y374X‐TDP‐43 ALS patients compared to controls; but in motor cortex (B) there was evidence of loss of TDP‐43 function leading to an excess of transcript variant 2. (C and D) Quantification of STMN2 expression in motor cortex tissue from a single patient with a Y374X mutation and five controls. Quantification included STMN2 protein normalised to α‐tubulin (C) and STMN2 mRNA (D) normalised to U1 snRNA. Across all measurements expression of STMN2 protein was correlated with expression of TDP‐43 (Pearson test, r ² = 0.9, p = 0.004). (E) Quantification of UNC13A mRNA expression normalised to U1 snRNA in motor cortex tissue from a single patient with a Y374X mutation and five controls