Mutations Position Table
PSEN2 R62 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| R62H |
AD : Benign, FTD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown. In two carriers, CSF biomarker levels were variable. |
In two carriers, CSF Aβ peptide levels were variable. In cells, unchanged Aβ42/Aβ40 ratio; unchanged Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF. |
Cruts et al., 1998; Gallo et al., 2010 |
| R62C |
AD : Benign | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown. |
Reduced levels of CSF Aβ43 and Aβ42, and increased Aβ40; decreased Aβ42/Aβ40 ratio in one carrier. |
Sleegers et al., 2004 |
There are two reported variants at codon 62 in the N-terminal region of PSEN2 that result in the replacement of the arginine at this position with either cysteine or histidine. It is not clear that either variant affects pathogenicity as neither has been shown to segregate with disease (either AD or FTD) in the families in which the variants were identified. Both variants have been found in cognitively healthy individuals. Notably, the R62H variant was found in 20 out of 130 African individuals whose DNA was included in the Centre d’Etude du Polymorphisme Humain-Human Genome Diversity Panel (CEPH-HGDP), suggesting this may be a common polymorphism in African populations.
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