Evidence map›Paper›PMID 32707200›Full record

ArticleAmerican journal of ophthalmology2021

Whole-Exome Sequencing of Patients With Posterior Segment Uveitis.

Angela S Li, Gabriel Velez, Benjamin Darbro, Marcus A Toral, Jing Yang, Stephen H Tsang, Polly J Ferguson, James C Folk, Alexander G Bassuk, Vinit B Mahajan

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of ophthalmology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Genetic Linkage betweenInternational journal of molecular sciences · 2024
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. UVB-Induced Skin Autoinflammation Due toFrontiers in immunology · 2022
    Article
  12. 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

10 authors at 3 institutions in 1 country.

Angela S LiMolecular Surgery Laboratory, Stanford University, Palo Alto, California, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California, USA.
Gabriel VelezMolecular Surgery Laboratory, Stanford University, Palo Alto, California, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California, USA; Medical Scientist Training Program, University of Iowa, Iowa City, Iowa, USA.
Benjamin DarbroDepartment of Pediatrics, Medical Genetics and Genomics, University of Iowa, Iowa City, Iowa, USA.
Marcus A ToralMolecular Surgery Laboratory, Stanford University, Palo Alto, California, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California, USA; Medical Scientist Training Program, University of Iowa, Iowa City, Iowa, USA.
Jing YangMolecular Surgery Laboratory, Stanford University, Palo Alto, California, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California, USA.
Stephen H TsangBarbara and Donald Jonas Laboratory of Stem Cells and Regenerative Medicine and Bernard & Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, Columbia University, New York, New York, USA; Department of Pathology & Cell Biology, College of Physicians & Surgeons (S.H.T.), Columbia University, New York, New York, USA.
Polly J FergusonDepartment of Pediatrics, Division of Pediatric Rheumatology, University of Iowa, Iowa City, Iowa, USA.
James C FolkDepartment of Ophthalmology, University of Iowa, Iowa City, Iowa, USA.
Alexander G BassukDepartment of Neurology and Pediatrics, University of Iowa, Iowa City, Iowa, USA.
Vinit B MahajanMolecular Surgery Laboratory, Stanford University, Palo Alto, California, USA; Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California, USA; Veterans Affairs, Palo Alto HCS, Palo Alto, California, USA. Electronic address: vinit.mahajan@stanford.edu.
University of Iowa · USPalo Alto University · USColumbia University · US

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007337 · NIGMS · UNIVERSITY OF IOWA · PI GEYER, PAMELA K., LENTZ, STEVEN R · 1985 to 2020
$15.9M
Instrumentation, Fabrication, and Design CoreP30EY019007 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Xin Zhang · 2010 to 2026
$12.9M
Stanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI Jeffrey L Goldberg · 2017 to 2026
$8.0M
Toward mechanism- and gene-based therapies for retinal degenerationR01EY018213 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Stephen H Tsang · 2008 to 2026
$6.6M
Gene Silencing and Gene Editing in PhototransductionR01EY024698 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Stephen H Tsang · 2015 to 2026
$4.7M
Genetic & immunologic etiology of chronic recurrent multifocal osteomyelitis-CRMOR01AR059703 · NIAMS · UNIVERSITY OF IOWA · PI BASSUK, ALEXANDER G, FERGUSON, POLLY J · 2010 to 2019
$3.5M
Structure and Function of Calpain-5R01EY024665 · NEI · UNIVERSITY OF IOWA · PI MAHAJAN, VINIT B · 2015 to 2019
$1.9M
Mechanistic Studies on Regenerative Medicine Approaches to Childhood BlindnessR01EY026682 · NEI · UNIVERSITY OF IOWA · PI BASSUK, ALEXANDER G, MAHAJAN, VINIT B · 2016 to 2019
$1.6M
Mechanism-based therapies for photoreceptor degenerationR01EY025225 · NEI · UNIVERSITY OF IOWA · PI MAHAJAN, VINIT B · 2015 to 2018
$1.3M
Evaluating GWAS AMD Candidate Loci by Gene Editing in Human iPS CellsR21AG050437 · NIA · UNIVERSITY OF IOWA · PI BASSUK, ALEXANDER G, MAHAJAN, VINIT B · 2015 to 2016
$431k
Structure-function studies of Calpain-5 in hereditary uveitisF30EY027986 · NEI · UNIVERSITY OF IOWA · PI VELEZ, GABRIEL · 2018 to 2021
$164k
NCI NIH HHS P30 CA013696NEI NIH HHS F30 EY027986NEI NIH HHS P30 EY019007NEI NIH HHS P30 EY026877NEI NIH HHS R01 EY018213NEI NIH HHS R01 EY024665NEI NIH HHS R01 EY024698NEI NIH HHS R01 EY025225NEI NIH HHS R01 EY026682NIAMS NIH HHS R01 AR059703NIA NIH HHS R21 AG050437NIGMS NIH HHS T32 GM007337
6 · The paper itself

Abstract

objectiveTo elucidate molecular risk factors for posterior segment uveitis using a functional genomics approach.

designGenetic association cohort study.

methodsSetting: Single-center study at an academic referral center. STUDY POPULATION: 164 patients with clinically diagnosed uveitis of the posterior segment.

main outcome measuresExome sequencing was used to detect variants identified in 164 patients with posterior segment uveitis. A phenotype-driven analysis, protein structural modeling, and in silico calculations were then used to rank and predict the functional consequences of key variants.

resultsA total of 203 single nucleotide variants, in 23 genes across 164 patients, were included in this study. Both known and novel variants were identified in genes previously implicated in specific types of syndromic uveitis-such as NOD2 (Blau syndrome) and CAPN5 NIV (neovascular inflammatory vitreoretinopathy)-as well as variants in genes not previously linked to posterior segment uveitis. Based on a ranked list and protein-protein-interaction network, missense variants in NOD-like receptor family genes (NOD2, NLRC4, NLRP3, and NLRP1), CAPN5, and TYK2 were characterized via structural modeling and in silico calculations to predict how specific variants might alter protein structure and function. The majority of analyzed variants were notably different from wild type.

conclusionsThis study implicates new pathways and immune signaling proteins that may be associated with posterior segment uveitis susceptibility. A larger cohort and functional studies will help validate the pathogenicity of the mutations identified. In specific cases, whole-exome sequencing can help diagnose nonsyndromic uveitis in patients harboring known variants for syndromic inflammatory diseases.

Indexed as

Exome SequencingAdolescentAdultAgedAged, 80 and overCalpainChildChild, PreschoolFemaleGenetic Association StudiesHumansInflammasomesMaleMiddle AgedMutation, MissenseNLR ProteinsCalpainCapn5 protein, humanInflammasomesNLR ProteinsTYK2 KinaseTYK2 protein, human

Identifiers

PMID32707200
PMCPMC7736069
OpenAlexW3044556977

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.