Topic: Brain proteins, microglia and lab models
Plain-language summary
Objective The objective of this study was to identify new causes of Charcot-Marie-Tooth (CMT) disease in patients with autosomal-recessive (AR) CMT. Methods To efficiently identify novel causative genes for AR-CMT, we analyzed 303 unrelated Japanese patients with CMT using whole-exome sequencing and extracted recessive variants/genes shared among multiple patients. We performed mutation screening of the newly identified membrane metalloendopeptidase (MME) gene in 354 additional patients with CMT. We clinically, genetically, pathologically, and radiologically examined 10 patients with the MME mutation. Results We identified recessive mutations in MME in 10 patients. The MME gene encodes neprilysin (NEP), which is well known to be one of the most prominent beta-amyloid (Aβ)-degrading enzymes. All patients had a similar phenotype consistent with late-onset axonal neuropathy. They showed muscle weakness, atrophy, and sensory disturbance in the lower extremities. All the MME mutations could be loss-of-function mutations, and we confirmed a lack/decrease of NEP protein expression in a peripheral nerve. No patients showed symptoms of dementia, and 1 patient showed no excess Aβ in Pittsburgh compound-B positron emission tomography imaging. Interpretation Our results indicate that loss-of-function MME mutations are the most frequent cause of adult-onset AR-CMT2 in Japan, and we propose that this new disease should be termed AR-CMT2T. A loss-of-function MME mutation did not cause early-onset Alzheimer's disease. Identifying the MME mutation responsible for AR-CMT could improve the rate of molecular diagnosis and the understanding of the molecular mechanisms of CMT.
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APA 7th
Higuchi, Y., Hashiguchi, A., Yuan, J., Yoshimura, A., Mitsui, J., Ishiura, H., et al. (2016). Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2. Annals of neurology. https://doi.org/10.1002/ana.24612
Vancouver
Higuchi Y, Hashiguchi A, Yuan J, Yoshimura A, Mitsui J, Ishiura H, et al. Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2. Annals of neurology. 2016. doi:10.1002/ana.24612. PMID: 26991897.
BibTeX
@article{higuchi2016-26991897,
author = {Higuchi, Y. and Hashiguchi, A. and Yuan, J. and Yoshimura, A. and Mitsui, J. and Ishiura, H. and Tanaka, M. and Ishihara, S. and others},
title = {{Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2}},
journal = {Annals of neurology},
year = {2016},
doi = {10.1002/ana.24612},
pmid = {26991897},
url = {https://doi.org/10.1002/ana.24612}
}
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Key findings
- Results We identified recessive mutations in MME in 10 patients.
- Interpretation Our results indicate that loss-of-function MME mutations are the most frequent cause of adult-onset AR-CMT2 in Japan, and we propose that this new disease should be termed AR-CMT2T.
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Study details
- Participants303
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / 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 and multicenter collaboration, so those were left out: it earned 30 of the 58 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of 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 | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 303 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26991897) |
| Free to read | 2 / 2 | Free to read |
| Points | 30 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 30 of the 58 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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