Discover the intricate relationship between clinical symptoms and pathological characteristics of Frontotemporal Dementia and Parkinsonism linked to chromosome 17 (FTDP-17) with a specific MAPT mutation, shedding light on its unique diagnostic and therapeutic challenges.
– by The Don
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Clinical and Pathological Features of FTDP-17 with MAPT p.K298_H299insQ Mutation.
Morino et al., Mov Disord Clin Pract 2024
<!– DOI: 10.1002/mdc3.14042 //–>
https://doi.org/10.1002/mdc3.14042
Let me tell you, folks, we’ve got something huge here. We’re talking about a gene, MAPT, that’s causing a big problem – frontotemporal dementia with parkinsonism linked to chromosome 17, or FTDP-17 for short. This isn’t just any disease; it’s a hereditary degenerative disease with a whole array of symptoms. We’re seeing things like progressive supranuclear palsy, corticobasal syndrome, Parkinson’s disease, and frontotemporal dementia. Incredible, right?
So, what did we do? We took a deep dive into the genetics of two families hit hard by this disease, looking at everything from linkage analysis to exome sequencing. And let me tell you, we didn’t stop there. We went all out with tau protein assays, heparin-induced tau aggregation, and even western blotting with brain lysate from an autopsy case. We’re talking top-notch, state-of-the-art research.
And guess what we found? A variant, c.896_897insACA, p.K298_H299insQ, right in the MAPT gene of affected patients. This is big news. Most of these patients started with atypical parkinsonism, but it didn’t stop there. The mutant tau protein? It’s not doing its job. It’s forming abnormal fibrous aggregates instead of polymerizing microtubules like it’s supposed to.
Pathologically speaking, we’re seeing some serious damage – frontotemporal lobe atrophy, midbrain atrophy, you name it. And those tau-positive inclusions in the hippocampus, brainstem, and spinal cord neurons? They’re a tell-tale sign of FTDP-17.
Let me be clear: this insACA mutation is the culprit behind FTDP-17. Patients might start off looking like they have Parkinson’s, but it evolves into something much more severe. And while the initial diagnosis might point towards frontotemporal dementia, the spread of lesions tells us it’s progressive supranuclear palsy we’re dealing with.
We’re on the brink of something huge here, folks. Studying more cases will not only shed light on the common pathogenesis of MAPT mutations but also help us understand the specific pathogeneses of each mutation. We’re making America great in medical research, one gene at a time.