Mutations Position Table
PSEN1 L166 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| L166P |
AD : Pathogenic, ALS-FTD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 6 | In one individual, numerous Aβ-positive neuritic and cotton-wool plaques throughout the cerebral cortex; abundant Aβ-positive amyloid cores in the cerebellar cortex. In another, robust amyloid pathology in the striatum and cerebellum, and asymmetric tau pathology in the primary sensorimotor cortex contralateral to the side most affected by spasticity. |
Decreased Aβ (37 + 38 + 40) / (42 + 43) and Aβ37/Aβ42 and increased Aβ42/Aβ40. Increased Aβ42 and Aβ43; endosomal accumulation of APP β-CTF. Also, interfered with wild-type PSEN1 activity, reduced GLT-1 interaction, inhibited calcium leak in the ER, affected ApoE secretion, altered PSEN1 subcellular localization. Stalled γ-secretase-substrate complex tied to synaptic loss. |
Moehlmann et al., 2002 |
| L166H |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 6 | Unknown; MRI showed marked hippocampal atrophy and cortical atrophy, especially in the insula and the peri-insular temporal lobe. SPECT imaging showed bilateral hypometabolism in the parietal and frontal lobes. |
Unknown, but multiple in silico algorithms predicted a damaging effect. |
Pantieri et al., 2005 |
| L166R |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 6 | Unknown; MRI in the proband showed cortical atrophy; PET showed parietal hypoperfusion. |
Unknown, but multiple in silico algorithms predicted a damaging effect. |
Ezquerra et al., 2000 |
| L166del |
AD : Not Classified | Deletion | Deletion | Deletion | Coding | Exon 6 | Unknown; MRI showed generalized, symmetrical cerebral atrophy, which was most prominent in the medial temporal lobes. |
Unknown. |
Knight et al., 2007 |
| L166V |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 6 | SPECT imaging performed four years after symptom onset showed temporoparietal hypoperfusion. Postmortem evaluation revealed neuropathology consistent with AD, including advanced plaques and tangles (CERAD C, Braak stage VI). |
Unknown; predicted damaging in silico by multiple algorithms. |
Sassi et al., 2014 |
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