Table 1.
Clinical, genealogical and genetic data of eight patients with MAPT p.P301L mutation
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | |
|---|---|---|---|---|---|---|---|---|
| Sex | F | M | M | M | F | F | M | M |
| Age of death (y) | 65 | 53 | 62 | 52 | 64 | 61 | 55 | 56 |
| Duration (y) | 12 | 3 | 8 | 10 | 8 | 11 | 5 | 14 |
| Initial presentation | personality/ behavior changes,short-term memory loss |
personality/ behavior changes, bradykinesia, hand tremor |
personality/ behavior changes |
personality/ behavior changes |
personality/behavi or changes |
personality/behavi or changes, mild cognitive impairment |
personality/behavi or changes |
short time memory loss, anomia |
| FTD type* | bvFTD | bvFTD | bvFTD | bvFTD | bvFTD | bvFTD | bvFTD | svPPA |
| Parkinsonism | bradykinesia, rigidity, hand tremor, postural instability, gait freezing, hypomimia |
rigidity, hand tremor, unsteady gait |
bradykinesia, unsteady gait, stooped posture |
none | arm rigidity, bradykinesia, reduced arm swing, hypomimia |
mild rigidity in upper limbs |
shuffling gait, multiple falls |
rigidity of right upper limb, hypomimia |
| Distribution of motor signs |
L > R | N/A | N/A | none | R > L | R = L | N/A | R>L |
| Other signs & symptoms |
long-term memory loss, dysphagia, secondary semantic dysfunction, dyscalculia, incontinence |
hallucinations, memory impairment, hyperphagia, incontinence |
paratonia, apraxia, epilepsy, secondary semantic dysfunction, incontinence |
mild cognitive decline |
secondary semantic dysfunction, reduced empathy, incontinence |
bilateral palmomental reflex, immobile, nonverbal (end stage) |
secondary semantic dysfunction |
poor hygiene, angry outbursts, food fads, epilepsy |
| Brain imaging | MRI (57y): ventriculo megaly; PET (54y): normal |
MRI (atrophy, no further details) |
MRI (60y): ventriculo- megaly, fronto- temporal atrophy; SPECT (60y): fronto- parietal & temporal hypoperfusion |
MRI (48y): frontotemporal atrophy L>R; PET (48y): frontotemporal hypometa- bolism |
MRI (60y): frontotemporal atrophy L> R, esp. L anterior temporal & hippocampal atrophy |
SPECT (55y): frontotemporal hypoperfusion; MRI (56y): frontotemporal atrophy R> L |
MRI (55y): moderate frontal & temporal atrophy, mild hippocampal atrophy |
MRI (49y): frontotemporal atrophy, left middle & anterior temporal |
| Family history of early onset dementia |
mother, maternal grandmother |
mother, several maternal aunts & uncles, cousin |
6 of 11 siblings, mother & maternal aunt |
mother, maternal grandfather & aunt |
father | father, 2 brothers, 2 paternal aunts, 3 cousins |
brother, sister, mother, maternal aunts, cousins |
father, brother, sister, 2 paternal aunts, 3 cousins |
| MAPT | H1/H1 | H1/H1 | H1/H2 | H1/H2 | H1/H2 | H1/H1 | H1/H2 | H1/H2 |
| APOE | ε3/ε3 | ε3/ε3 | ε3/ε4 | ε3/ε3 | ε3/ε3 | ε3/ε3 | ε3/ε3 | ε3/ε3 |
Abbreviations.
*
defined on the basis of leading features at the initial clinical presentation;
APOE = apolipoprotein E gene; bvFTD = behavioral variant frontotemporal dementia; ε = epsilon (APOE allele); FTD = frontotemporal dementia; L = left; MAPT = microtubule-associated protein tau gene; MRI = magnetic resonance imaging; N/A = not available; PET (FDG-PET) = fludeoxyglucose positron emission tomography; R = right; SPECT (99mTc-HMPAO SPECT) = technetium hexamethylpropylene amine oxime single-photon emission computed tomography; svPPA = semantic variant of primary progressive aphasia; y = years (old)