Background: The IVS10+14 mutation in the microtubule-associated protein tau gene, MAPT, is a rare point mutation that dysregulates tau splicing resulting in pathological aggregation. This mutation has been identified in three families with severe neurodegenerative disease. We characterized the clinicopathological features of a fourth, Canadian family with the IVS10+14 MAPT mutation and compared them to previously reported families. Methods: Clinical and neuropathological records from three family members with the IVS10+14 MAPT mutation were reviewed. Neuropathological section from one available case were analyzed. Results: Considerable interfamilial phenotypic heterogeneity is reported in all cohorts that express the IVS10+14 MAPT mutation, with prominent motor, cognitive, behavioural, and respiratory symptoms. The Canadian cohort also expressed profound sensory and sleep abnormalities, not reported previously. In the two siblings with available neuropathological records, neuropathological changes ranged from mild to severe. Conclusions: All families expressing the IVS10+14 MAPT mutation display striking inter- and intrafamilial clinical and neuropathologic phenotypic variability. Our cohort adds sensory and sleep abnormalities as potential symptoms and illustrates a lack of clear clinicopathological correlates for these heterogenous symptoms.

Reference: Maxwell et al. 2021. Clinical and Neuropathological Variability in the Rare IVS10+14 Tau Mutation. Neurobiology of Aging. In Press. DOI: 10.1016/j.neurobiolaging.2021.01.004.