Mutations Position Table

PSEN1 H163 Mutations

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Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
H163P
Alzheimer's Disease Alzheimer's Disease : Unclear Pathogenicity

Brain biopsy of the frontal cortex showed numerous senile plaques and neurofibrillary tangles compatible with a diagnosis of AD. No spongiform changes or abnormal prion protein were detected.

Unknown.


Coding
Exon 5
Point, Missense
CAT to CCT
0 Kim 2012
H163R
Alzheimer's Disease, Myoclonus Alzheimer's Disease : Pathogenic

Data are limited, but neuropathology consistent with AD has been observed in at least one case.

Elevated Aβ42/Aβ total ratio in COS-1 cells. Affects γ-secretase-dependent neurexin processing.

[MET1] g.38785A>G
[NT1] g.55390A>G
rs63750590
Coding
Exon 5
Point, Missense
CAT to CGT
1 Campion 1995;
Sherrington 1995;
Tanahashi 1995
H163Y
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Unknown; decreased glucose metabolism in presymptomatic mutation carriers, especially in the thalamus.

Increased Aβ42/Aβ total ratio when expressed in COS-1 cells co-transfected with APP695.

[MET1] g.38784C>T
[NT1] g.55389C>T
rs63749885
Coding
Exon 5
Point, Missense
CAT to TAT
0 1995

Three different missense mutations have been described which are predicted to cause amino acid substitutions at position 163. H163R and H163Y were discovered early (1995), whereas H163P was not reported until nearly 20 years later. In addition, whereas H163R is among the most frequently observed AD mutations in diverse populations, H163P has been reported in a single individual, with an intermediate reported frequency for H163Y. Age of onset varies as well, ranging from 37–52 years for H163R, 44-65 years for H163Y, and 33 years for the single H163 patient.

Although individuals with mutations at this position meet clinical criteria for AD, atypical AD symptoms were frequently reported, including early- or late-stage myoclonus and seizures, as well as aphasia, spasticity, and pyramidal signs.