We found that CLP1, each of the known TSENs, and HSPC117 were expressed ubiquitously in 14 human tissues and ages tested (Figure S2B), suggesting a conserved function. Therefore, to understand the selective cellular vulnerability, we generated induced neurons (iNeurons) from affected and unaffected fibroblasts, using recently published methods (Xue et al., 2013), yielding approximately 80% neural cells in culture (Figure S2C-E). Both patient fibroblasts and iNeurons showed reduced nuclear localized CLP1, supported by nuclear/cytoplasmic fibroblast cell fractionation (Figure 2D-E). We conclude that the p.R140H mutation results in both failed nuclear localization and impaired kinase activity, as a mechanism of impaired function.
