Table 2 Clinical features of GRN p.V490M family patients and other pathogenic GRN missense mutations
From: A novel c.1468 G > A GRN mutation causes frontotemporal dementia in a Chinese Han family
Mutation | Family history | Affected (n) | Age at onset(y) | Clinical diagnosis | Clinical symptoms | CT/MRI | FDG/Aβ/Tau-PET | Pathology | PGRN plasma level (ng/ml) | APOE | |
|---|---|---|---|---|---|---|---|---|---|---|---|
p.V490M* | Yes | 3 | II:2 | 70 | Probable AD | Memory and cognitive impairment, cataphasia | H-T atrophy | N | N | N | NA |
II:3 | 69 | Probable AD | Memory loss, cognitive impairment | H–T atrophy, cortical and subcortical atrophy | N | CSF biomarkers consistent with AD | N | ε3/ε3 | |||
II:5 | 67 | MCI | Mild cognitive impairment | Mild cortex atrophy without H | T (R)-P (L) hypo-metabolism Aβ-PET negative | N | N | ε3/ε3 | |||
p.C139R | Yes | 2 | II:9 | 77 | AD | Memory decline and impairment of instrumental activities | F–T atrophy | N | N | N | ε3/ε3 |
II:10 | 75 | AD | Memory impairment, spatial and temporal disorientation, prosopagnosia | F–T atrophy(L > R) | N | Brain autopsy presented the pathologic hallmarks of AD | 96 | ε3/ε3 | |||
p.V500I | No | 1 | 55 | bvFTD, PSP | Vertical supranuclear gaze palsy, rigidity and postural tremor of right upper limb, progressive memory deterioration | Mild cortex atrophy | Mild hypo-metabolism in bilateral frontotemporal lobe | p.V500I mutation over-expression increases apoptosis of SH-SY5Y cells | N | N | |
p.A324T | No | 1 | 64 | PNFA | Apraxia of speech | T-P atrophy(L > R) | N | Brain autopsy presented the pathologic hallmarks of CBD | NA | N | |
p.W7R | Yes | 1 | 53 | bvFTD | Behavioral change, apathy, loss of empathy, indifference, social withdrawal | F–T–P atrophy (L > R) | severe hypo-metabolism in prefrontal, orbitofrontal, cingulate cortex, temporal pole, and temporoparietal junction | The mutation leads to progranulin haploinsufficiency | 41 | N | |