Mutations Position Table
PSEN1 G206 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| G206A |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 7 | Typical AD neuropathology, including extensive plaques and tangles (Braak stage VI). Cortical atrophy revealed by MRI and temporo-parietal hypometabolism revealed by FDG-PET. In one case, MRI alterations were similar to those of limbic encephalitis. |
Increased Aβ42/Aβ40 ratio, decreased Aβ37/Aβ42 ratio. γ-secretase activity = 61% of wildtype.
|
Rogaeva et al., 2001; Athan et al., 2001 |
| G206D |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 7 | Neuropathology consistent with AD. |
Increased Aβ42 production; reduced interaction with Pen2; disrupted ER calcium homeostasis. |
Raux et al., 2005 |
| G206V |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 7 | Unknown; an early MRI of the proband showed mild atrophy of the brain with normal temporal lobes. |
Increased total Aβ and Aβ42, and decreased Aβ43, Aβ40, and Aβ38 in cells. |
Goldman et al., 2002 |
| G206R |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 7 | Consistent with AD. Also, end-stage TDP-43 and severe α-synuclein pathologies. |
Unknown, but in silico algorithm suggests deleterious (PHRED scaled-CADD = 29.2). |
Libard et al., 2022 |
| G206S |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 7 | Unknown; bilateral frontotemporal and parietal hypometabolism by PET; diffuse brain atrophy with enlarged ventricles by CT. |
Decreased Aβ40 and Aβ42 production; increased Aβ42/Aβ40 ratio in vitro. |
Rogaeva et al., 2001; Raux et al., 2005 |
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