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67/100

✓ Peer-reviewed alzhub usefulness score 67 out of 100. Disparities

Topic: Brain proteins, microglia and lab models

Background We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion. Findings In patients with sporadic ALS, we identified the repeat expansion in 236 (7·0%) of 3377 white individuals from the USA, Europe, and Australia, two (4·1%) of 49 black individuals from the USA, and six (8·3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39·3%) of 552 white individuals with familial ALS from Europe and the USA. 59 (6·0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24·8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic ALS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years. Interpretation A common Mendelian genetic lesion in C9orf72 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases. Funding Full funding sources listed at end of paper (see Acknowledgments).

Key findings

Background We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Why it matters

This study found that a C9orf72 repeat expansion is present in a substantial share of people with ALS and FTD, including many with no family history. It does not test any treatment or prevention, so it only helps identify who might carry this genetic cause.

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Study details

Participants4,448
Evidence strengthLow

How this study scored 67/100

Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (The Lancet. Neurology)
Journal's citation record	3 / 4	The Lancet Neurology: journal h-index 457 (OpenAlex, 2026-10-29)
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	2012 — within 20 year(s) of the newest study here
Sample size	3 / 4	4,448 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 / 7	Cited 1,214 times (OpenAlex, 2026-10-10)
Citations per year	5 / 5	75.9 citations a year over 16 year(s) since 2012
Impact for its field and year	6 / 6	Cited 66.5× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	3 / 6	Cited by 27 other studies in this library
Still being cited	3 / 4	Cited 190 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author Bryan J. Traynor: h-index 92 (OpenAlex, whole career)
Institution's track record	3 / 3	National Institutes of Health: institution h-index 2,723 (OpenAlex)
Multi-centre collaboration	3 / 3	OpenAlex lists 49 institution(s) in 12 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 22406228)
Free to read	2 / 2	Free to read
Total	67 / 100	—

What each of these 20 components measures, and what this score is not →

Read the original

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. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.

APA 7th

Majounie, E., Renton, A. E., Mok, K., Dopper, E. G., Waite, A., Rollinson, S., et al. (2012). Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. The Lancet. Neurology. https://doi.org/10.1016/s1474-4422(12)70043-1

Vancouver

Majounie E, Renton AE, Mok K, Dopper EG, Waite A, Rollinson S, et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. The Lancet. Neurology. 2012. doi:10.1016/s1474-4422(12)70043-1. PMID: 22406228.

BibTeX

@article{majounie2012-22406228,
  author  = {Majounie, E. and Renton, A. E. and Mok, K. and Dopper, E. G. and Waite, A. and Rollinson, S. and Chiò, A. and Restagno, G. and others},
  title   = {{Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study}},
  journal = {The Lancet. Neurology},
  year    = {2012},
  doi     = {10.1016/s1474-4422(12)70043-1},
  pmid    = {22406228},
  url     = {https://doi.org/10.1016/s1474-4422(12)70043-1}
}

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