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Genetic screening in early-onset Alzheimer's disease identified three novel presenilin mutations
Tsz Hang Wong, Harro Seelaar, Shamiram Melhem, Annemieke J M Rozemuller, John C van Swieten. Neurobiology of aging, 2019-01-29
Topic: Genetics and APOE
Mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) are major genetic causes of early-onset Alzheimer's disease (EOAD). Clinical heterogeneity is frequently observed in patients with PSEN1 and PSEN2 mutations. Using whole exome sequencing, we screened a Dutch cohort of 68 patients with EOAD for rare variants in Mendelian Alzheimer's disease, frontotemporal dementia, and prion disease genes. We identified 3 PSEN1 and 2 PSEN2 variants. Three variants, 1 in PSEN1 (p.H21Profs*2) and both PSEN2 (p.A415S and p.M174I), were novel and absent in control exomes. These novel variants can be classified as probable pathogenic, except for PSEN1 (p.H21Profs*2) in which the pathogenicity is uncertain. The initial clinical symptoms between mutation carriers varied from behavioral problems to memory impairment. Our findings extend the mutation spectrum of EOAD and underline the clinical heterogeneity among PSEN1 and PSEN2 mutation carriers. Screening for Alzheimer's disease-causing genes is indicated in presenile dementia with an overlapping clinical diagnosis.
Key findings
- Our findings extend the mutation spectrum of EOAD and underline the clinical heterogeneity among PSEN1 and PSEN2 mutation carriers.
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Study details
- Participants68
- Evidence strengthModerate
How this study scored 50/100
Published in a peer-reviewed journal. Scored zero for study design, 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 28 of the 56 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of 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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 68 participants |
| 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 (participant count stated) |
| 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 30797548) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 28 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 28 of the 56 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
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APA 7th
Wong, T. H., Seelaar, H., Melhem, S., Rozemuller, A. J. M., & van Swieten, J. C. (2020). Genetic screening in early-onset Alzheimer's disease identified three novel presenilin mutations. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2019.01.015
Vancouver
Wong TH, Seelaar H, Melhem S, Rozemuller AJM, van Swieten JC. Genetic screening in early-onset Alzheimer's disease identified three novel presenilin mutations. Neurobiology of aging. 2020. doi:10.1016/j.neurobiolaging.2019.01.015. PMID: 30797548.
BibTeX
@article{wong2020-30797548,
author = {Wong, Tsz Hang and Seelaar, Harro and Melhem, Shamiram and Rozemuller, Annemieke J M and van Swieten, John C},
title = {{Genetic screening in early-onset Alzheimer's disease identified three novel presenilin mutations}},
journal = {Neurobiology of aging},
year = {2020},
doi = {10.1016/j.neurobiolaging.2019.01.015},
pmid = {30797548},
url = {https://doi.org/10.1016/j.neurobiolaging.2019.01.015}
}
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