Evidence map›Paper›PMID 26740678›Full record

ArticleNeurology2016

OPTN 691_692insAG is a founder mutation causing recessive ALS and increased risk in heterozygotes.

Orly Goldstein, Omri Nayshool, Beatrice Nefussy, Bryan J Traynor, Alan E Renton, Mali Gana-Weisz, Vivian E Drory, Avi Orr-Urtreger

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In one paragraph

Article in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Modelling amyotrophic lateral sclerosis in rodents.Nature reviews. Neuroscience · 2022
    Review
  9. Genes · 2021
    Article
  10. Article
  11. Review
  12. Novel mutation in optineurin causing aggressive ALS+/-frontotemporal dementia.Annals of clinical and translational neurology · 2019
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. The genetics of amyotrophic lateral sclerosis: current insights.Degenerative neurological and neuromuscular disease · 2016
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Orly GoldsteinFrom The Genetic Institute (O.G., O.N., M.G.-W., A.O.-U.) and the Neuromuscular Service, Department of Neurology (B.N., V.E.D.), Tel Aviv Sourasky Medical Center, Israel; the Laboratory of Neurogenetics (B.J.T., A.E.R.), National Institute on Aging, Bethesda, MD; and the Sackler Faculty of Medicine (V.E.D., A.O.-U.), Tel Aviv University, Israel.
Omri NayshoolFrom The Genetic Institute (O.G., O.N., M.G.-W., A.O.-U.) and the Neuromuscular Service, Department of Neurology (B.N., V.E.D.), Tel Aviv Sourasky Medical Center, Israel; the Laboratory of Neurogenetics (B.J.T., A.E.R.), National Institute on Aging, Bethesda, MD; and the Sackler Faculty of Medicine (V.E.D., A.O.-U.), Tel Aviv University, Israel.
Beatrice NefussyFrom The Genetic Institute (O.G., O.N., M.G.-W., A.O.-U.) and the Neuromuscular Service, Department of Neurology (B.N., V.E.D.), Tel Aviv Sourasky Medical Center, Israel; the Laboratory of Neurogenetics (B.J.T., A.E.R.), National Institute on Aging, Bethesda, MD; and the Sackler Faculty of Medicine (V.E.D., A.O.-U.), Tel Aviv University, Israel.
Bryan J TraynorFrom The Genetic Institute (O.G., O.N., M.G.-W., A.O.-U.) and the Neuromuscular Service, Department of Neurology (B.N., V.E.D.), Tel Aviv Sourasky Medical Center, Israel; the Laboratory of Neurogenetics (B.J.T., A.E.R.), National Institute on Aging, Bethesda, MD; and the Sackler Faculty of Medicine (V.E.D., A.O.-U.), Tel Aviv University, Israel.
Alan E RentonFrom The Genetic Institute (O.G., O.N., M.G.-W., A.O.-U.) and the Neuromuscular Service, Department of Neurology (B.N., V.E.D.), Tel Aviv Sourasky Medical Center, Israel; the Laboratory of Neurogenetics (B.J.T., A.E.R.), National Institute on Aging, Bethesda, MD; and the Sackler Faculty of Medicine (V.E.D., A.O.-U.), Tel Aviv University, Israel.
Mali Gana-WeiszFrom The Genetic Institute (O.G., O.N., M.G.-W., A.O.-U.) and the Neuromuscular Service, Department of Neurology (B.N., V.E.D.), Tel Aviv Sourasky Medical Center, Israel; the Laboratory of Neurogenetics (B.J.T., A.E.R.), National Institute on Aging, Bethesda, MD; and the Sackler Faculty of Medicine (V.E.D., A.O.-U.), Tel Aviv University, Israel.
Vivian E DroryFrom The Genetic Institute (O.G., O.N., M.G.-W., A.O.-U.) and the Neuromuscular Service, Department of Neurology (B.N., V.E.D.), Tel Aviv Sourasky Medical Center, Israel; the Laboratory of Neurogenetics (B.J.T., A.E.R.), National Institute on Aging, Bethesda, MD; and the Sackler Faculty of Medicine (V.E.D., A.O.-U.), Tel Aviv University, Israel.
Avi Orr-UrtregerFrom The Genetic Institute (O.G., O.N., M.G.-W., A.O.-U.) and the Neuromuscular Service, Department of Neurology (B.N., V.E.D.), Tel Aviv Sourasky Medical Center, Israel; the Laboratory of Neurogenetics (B.J.T., A.E.R.), National Institute on Aging, Bethesda, MD; and the Sackler Faculty of Medicine (V.E.D., A.O.-U.), Tel Aviv University, Israel. aviorr@tasmc.health.gov.il.
National Institute on Aging · US

Funding

Genome wide SNP analysis in Amyotrophic Lateral SclerosisZIAAG000933 · NIA · NATIONAL INSTITUTE ON AGING · PI TRAYNOR, BRYAN · 2009 to 2025
$9.8M
Genome wide SNP analysis in Parkinson's diseaseZ01AG000949 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW B · 2006 to 2008
$2.6M
Intramural NIH HHSNIA NIH HHS Z01-AG000949-02
6 · The paper itself

Abstract

objectiveTo detect genetic variants underlying familial and sporadic amyotrophic lateral sclerosis (ALS).

methodsWe analyzed 2 founder Jewish populations of Moroccan and Ashkenazi origins and ethnic matched controls. Exome sequencing of 2 sisters with ALS from Morocco was followed by genotyping the identified causative null mutation in 379 unrelated patients with ALS and 1,000 controls. The shared risk haplotype was characterized using whole-genome single nucleotide polymorphism array.

resultsWe identified 5 unrelated patients with ALS homozygous for the null 691_692insAG mutation in the optineurin gene (OPTN), accounting for 5.8% of ALS of Moroccan origin and 0.3% of Ashkenazi. We also identified a high frequency of heterozygous carriers among patients with ALS, 8.7% and 2.9%, respectively, compared to 0.75% and 1.0% in controls. The risk of carriers for ALS was significantly increased, with odds ratio of 13.46 and 2.97 in Moroccan and Ashkenazi Jews, respectively. We determined that 691_692insAG is a founder mutation in the tested populations with a minimal risk haplotype of 58.5 Kb, encompassing the entire OPTN gene.

conclusionsOur data show that OPTN 691_692insAG mutation is a founder mutation in Moroccan and Ashkenazi Jews. This mutation causes autosomal recessive ALS and significantly increases the risk to develop the disease in heterozygous carriers, suggesting both a recessive mode of inheritance and a dominant with incomplete penetrance. These data emphasize the important role of OPTN in ALS pathogenesis, and demonstrate the complex genetics of ALS, as the same mutation leads to different phenotypes and appears in 2 patterns of inheritance.

Indexed as

Founder EffectHeterozygoteAdultAgedAged, 80 and overAmyotrophic Lateral SclerosisCell Cycle ProteinsFemaleGenetic Predisposition to DiseaseHumansJewsMaleMembrane Transport ProteinsMiddle AgedMoroccoMutation, MissenseCell Cycle ProteinsMembrane Transport ProteinsOPTN protein, humanTranscription Factor TFIIIA

Identifiers

PMID26740678
PMCPMC4773945
OpenAlexW2233235415

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.