Frontotemporal lobar degeneration (FTLD) is the one of the most frequent neurodegenerative disorders characterized by behavioral and executive impairment, language disorders and motor dysfunction. Hereditary forms of FTLD are frequently reported and about 20-30% of cases exhibit an autosomal dominant transmission. Microtubule associate protein tau (MAPT) gene mutations are associated with early onset FTLD. Here we have identified a new MAPT mutation on exon 10 that alters both the protein function and the RNA alternative splicing. Biochemical and neuropathological studies indicate a high pathogenicity of this new MAPT mutation. Moreover induced neurons transdifferentiated from patient skin-derived fibroblasts and carrying the new MAPT mutation express both 3R and 4R tau isoforms differently from those obtained from embryonic fibroblasts which express only 3R tau isoform indicating that they are not mature neurons.
- K298E MAPT mutation
- Human induced-neurons