Two pathologically confirmed cases of novel mutations in the MAPT gene causing frontotemporal dementia

MAPT mutations were the first discovered genetic cause of frontotemporal dementia (FTD) in 1998. Since that time, over 60 MAPT mutations have been identified, usually causing behavioral variant FTD and/or parkinsonism clinically. We describe 2 novel MAPT mutations, D252V and G389_I392del, each presenting in a patient with behavioral variant FTD and associated language and cognitive deficits. Neuroimaging revealed asymmetrical left greater than right temporal lobe atrophy in the first case, and bifrontal atrophy in the second case. Disease duration was 8 years and 5 years, respectively. Postmortem examination in both patients revealed a 3-repeat predominant tauopathy, similar in appearance to Pick's disease. These 2 mutations add to the literature on genetic FTD, both presenting with similar clinical and imaging features to previously described cases, and pathologically showing a primary tauopathy similar to a number of other MAPT mutations.