Mutations Position Table

PSEN1 L166 Mutations

Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
L166del
Alzheimer's Disease Alzheimer's Disease : Not Classified

Unknown; MRI showed generalized, symmetrical cerebral atrophy, which was most prominent in the medial temporal lobes.

Unknown.

rs63751458
Coding
Exon 6
Deletion
CTT to ---
0 Knight et al., 2007
L166H
Alzheimer's Disease Alzheimer's Disease : Not Classified

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.

rs63750265
Coding
Exon 6
Point, Missense
CTT to CAT
0 Pantieri et al., 2005
L166P
Alzheimer's Disease, Spastic Paraparesis Alzheimer's Disease : Pathogenic

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.

Increased Aβ42 and Aβ43, decreased total Aβ production. Normal endoproteolysis. Reduced Notch and N-cadherin cleavage. Disrupts endosomes via accumulation of APP β-CTF. Also, dominant-negative effect on wild-type PSEN1, and inhibition of calcium leak in the ER. 

rs63750265
Coding
Exon 6
Point, Missense
CTT to CCT
4 Moehlmann et al., 2002
L166R
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Unknown; MRI in the proband showed cortical atrophy; PET showed parietal hypoperfusion.

Unknown, but multiple in silico algorithms predicted a damaging effect.

rs63750265
Coding
Exon 6
Point, Missense
CTT to CGT
0 Ezquerra et al., 2000
L166V
Alzheimer's Disease Alzheimer's Disease : Pathogenic

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.


Coding
Exon 6
Point, Missense
CTT to GTT
0 Sassi et al., 2014

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