MAPT Gene Mutation Types
Placeholder: short overview of MAPT mutation classes.
- 17q21.31: Gene locus (Placeholder subtext)
- 50+: Known mutations (Placeholder subtext)
- P301L: Common variant (Placeholder subtext)
- 9–13: Exons affected (Placeholder subtext)
Missense vs splice-site MAPT mutations
Placeholder: missense and intronic splice-site mutation categories.
Mutation hotspot regions
Placeholder: microtubule-binding repeat domain hotspots.
Tau Isoform Ratio Disruption
Placeholder: short overview of 3R/4R tau imbalance.
- ~1:1: Normal 3R:4R ratio (Placeholder subtext)
- Altered: Exon 10 splicing (Placeholder subtext)
- Increased: 4R-tauopathy shift (Placeholder subtext)
- Higher: Aggregation propensity (Placeholder subtext)
Exon 10 alternative splicing
Placeholder: exon 10 inclusion/exclusion mechanism.
Consequences of isoform skew
Placeholder: downstream microtubule and aggregation effects.
Frontotemporal-Lobe-Selective Tangle Accumulation
Placeholder: short overview of region-selective pathology.
- Frontal/temporal: Primary regions (Placeholder subtext)
- Hyperphosphorylated tau: Tangle composition (Placeholder subtext)
- Focal → diffuse: Spread pattern (Placeholder subtext)
- Regionally selective: Neuron loss (Placeholder subtext)
Why frontal and temporal lobes
Placeholder: regional vulnerability explanation.
Tangle formation timeline
Placeholder: progression stages of tangle spread.
Genetic vs Sporadic FTD Distinction
Placeholder: short overview comparing genetic and sporadic FTD.
- ~30–50%: Familial FTD share (Placeholder subtext)
- ~10–20%: MAPT-linked cases (Placeholder subtext)
- Variable: Sporadic onset age (Placeholder subtext)
- More predictable: Genetic onset age (Placeholder subtext)
Distinguishing clinical features
Placeholder: clinical clues separating genetic and sporadic FTD.
Other FTD genes besides MAPT
Placeholder: GRN and C9orf72 comparison note.
Genetic Counseling and Family Testing
Placeholder: short overview of counseling and predictive testing.
- Autosomal dominant: Inheritance mode (Placeholder subtext)
- ~50%: Offspring risk (Placeholder subtext)
- Available: Predictive testing (Placeholder subtext)
- Pre/post-test: Counseling step (Placeholder subtext)
Predictive testing process
Placeholder: pre-test and post-test counseling steps.
Family pedigree assessment
Placeholder: pedigree-based risk assessment note.