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A pathogenic PSEN2 p.His169Asn mutation associated with early-onset Alzheimer's disease
Vo Van Giau, Jung-Min Pyun, Eva Bagyinszky, Seong Soo A An, SangYun Kim. Clinical interventions in aging, 2018-07-31
Topic: Genetics and APOE
A pathogenic mutation in the PSEN2 gene in a Korean patient associated with EOAD was identified. Targeted Next-generation sequencing and Sanger sequencing revealed a heterozygous C to A transition at position 505 (c.505C>A), resulting in a probably missense mutation at codon 169 (p.His169Asn) in PSEN2. PolyPhen-2 and SIFT software analyses predicted this mutation to be a probable damaging variant. This hypothesis was supported by the results of 3D in silico modelling analyses that predicted the p.His169Asn may result in major helix torsion due to histidine to asparagine substitution. Mutation may cause additional stresses with hydrophobic residues on the surface that interact inside the transmembrane domain III, which is a conserved domain in PSEN2 His169. These findings revealed that the p.His169Asn might be an important residue in PSEN2, which may alter the functions of PSEN2, suggesting its potential involvement with AD phenotype. Future functional studies are needed to evaluate the role of PSEN2 p.His169Asn mutation in AD disease progression.
Key findings
- A pathogenic mutation in the PSEN2 gene in a Korean patient associated with EOAD was identified.
- Targeted Next-generation sequencing and Sanger sequencing revealed a heterozygous C to A transition at position 505 (c.505C>A), resulting in a probably missense mutation at codon 169 (p.His169Asn) in PSEN2.
- PolyPhen-2 and SIFT software analyses predicted this mutation to be a probable damaging variant.
- This hypothesis was supported by the results of 3D in silico modelling analyses that predicted the p.His169Asn may result in major helix torsion due to histidine to asparagine substitution.
- Mutation may cause additional stresses with hydrophobic residues on the surface that interact inside the transmembrane domain III, which is a conserved domain in PSEN2 His169.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 25 of the 56 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Clinical interventions in aging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30104866) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 25 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 25 of the 56 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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APA 7th
Van Giau, V., Pyun, J.-M., Bagyinszky, E., An, S. S. A., & Kim, S. (2018). A pathogenic PSEN2 p.His169Asn mutation associated with early-onset Alzheimer's disease. Clinical interventions in aging. https://doi.org/10.2147/cia.s170374
Vancouver
Van Giau V, Pyun J.-M, Bagyinszky E, An SSA, Kim S. A pathogenic PSEN2 p.His169Asn mutation associated with early-onset Alzheimer's disease. Clinical interventions in aging. 2018. doi:10.2147/cia.s170374. PMID: 30104866.
BibTeX
@article{vangiau2018-30104866,
author = {Van Giau, Vo and Pyun, Jung-Min and Bagyinszky, Eva and An, Seong Soo A and Kim, SangYun},
title = {{A pathogenic PSEN2 p.His169Asn mutation associated with early-onset Alzheimer's disease}},
journal = {Clinical interventions in aging},
year = {2018},
doi = {10.2147/cia.s170374},
pmid = {30104866},
url = {https://doi.org/10.2147/cia.s170374}
}