Mutations Position Table
PSEN1 L381 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| L381F |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 11 | Neuropathology consistent with AD, including neuritic amyoid plaques and neurofibrillary tangles. Hirano bodies and granulovacuolar degeneration in the hippocampus. |
In silico analysis suggests that the mutation affects the folding free energy and flexibility of the protein. |
Dolzhanskaya et al., 2014 |
| L381V |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 11 | Unknown, but in one carrier, PET revealed widespread amyloid and tau pathology, atrophy, hypometabolism, and reduced dopamine transporter in the putamen. In another, Aβ38 and Aβ40 in CSF were proportionately reduced while Aβ43 was relatively high resulting in an elevated Aβ43/Aβ42 ratio. |
Increased Aβ42/Aβ40 ratio; increased Aβ42 and Aβ43; Reduced PSEN1 N-terminal fragment (NTF), suggesting impaired endoproteolysis of PSEN1. |
Dintchov Traykov et al., 2009; Mehrabian et al., 2004 |
There are two missense mutations reported at position 381 in presenilin-1 that involve the substitution of leucine with either phenylalanine or valine. The L381F mutation appears to be a rare cause of disease, reported in one family. This family developed a very early onset and rapidly progressing form of dementia with neuropathology consistent with AD; however, other clinical findings were consistent with Kufs disease, an adult-onset form of neuronal ceroid lipofuscinoses (NCL)(Dolzhanskaya et al., 2013).
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