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Repeat expansion diseases
Paulson H.. Handbook of clinical neurology, 2018-01-01
Topic: Brain proteins, microglia and lab models
More than 40 diseases, most of which primarily affect the nervous system, are caused by expansions of simple sequence repeats dispersed throughout the human genome. Expanded trinucleotide repeat diseases were discovered first and remain the most frequent. More recently tetra-, penta-, hexa-, and even dodeca-nucleotide repeat expansions have been identified as the cause of human disease, including some of the most common genetic disorders seen by neurologists. Repeat expansion diseases include both causes of myotonic dystrophy (DM1 and DM2), the most common genetic cause of amyotrophic lateral sclerosis/frontotemporal dementia (C9ORF72), Huntington disease, and eight other polyglutamine disorders, including the most common forms of dominantly inherited ataxia, the most common recessive ataxia (Friedreich ataxia), and the most common heritable mental retardation (fragile X syndrome). Here I review distinctive features of this group of diseases that stem from the unusual, dynamic nature of the underlying mutations. These features include marked clinical heterogeneity and the phenomenon of clinical anticipation. I then discuss the diverse molecular mechanisms driving disease pathogenesis, which vary depending on the repeat sequence, size, and location within the disease gene, and whether the repeat is translated into protein. I conclude with a brief clinical and genetic description of individual repeat expansion diseases that are most relevant to neurologists.
Key findings
- I conclude with a brief clinical and genetic description of individual repeat expansion diseases that are most relevant to neurologists.
Why it matters
This review covers more than 40 diseases caused by expansions of simple sequence repeats, including C9ORF72 in ALS/frontotemporal dementia and Huntington disease, and discusses their varied molecular mechanisms. It provides clinical and genetic descriptions but reports no treatment, cure, or prevention for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, so that was left out: it earned 47 of the 96 points we could judge it on, which is 49 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Handbook of clinical neurology) |
| 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 | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 428 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 42.8 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 6 / 6 | Cited 53.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 164 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Henry Lauris Paulson: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Michigan: institution h-index 2,240 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29325606) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 47 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 47 of the 96 points we could judge it on is 49 out of 100. |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/b978-0-444-63233-3.00009-9
- PubMed: 29325606
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Paulson, H. (2018). Repeat expansion diseases. Handbook of clinical neurology. https://doi.org/10.1016/b978-0-444-63233-3.00009-9
Vancouver
Paulson H. Repeat expansion diseases. Handbook of clinical neurology. 2018. doi:10.1016/b978-0-444-63233-3.00009-9. PMID: 29325606.
BibTeX
@article{paulson2018-29325606,
author = {Paulson, H.},
title = {{Repeat expansion diseases}},
journal = {Handbook of clinical neurology},
year = {2018},
doi = {10.1016/b978-0-444-63233-3.00009-9},
pmid = {29325606},
url = {https://doi.org/10.1016/b978-0-444-63233-3.00009-9}
}
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