Evidence map›Paper›PMID 34076366›Full record

ArticleMolecular genetics & genomic medicine2021

Ending a diagnostic odyssey: Moving from exome to genome to identify cockayne syndrome.

Jennifer Friedman, Lynne M Bird, Richard Haas, Shira L Robbins, Shareef A Nahas, David P Dimmock, Matthew J Yousefzadeh, Mariah A Witt, Laura J Niedernhofer, Shimul Chowdhury

Registry-linked trialOpen access · goldAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular genetics & genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03385876 (Rapid Whole Genome Sequencing), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 48% 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.

NCT03385876 naenrolling by invitationnot on this map

Rapid Whole Genome Sequencing (rWGS): Rapid Genomic Sequencing for Acutely Ill Patients and the Collection, Storage, Analysis, and Distribution of Biological Samples, Genomic and Clinical Data

TypeinterventionalSponsorRady Pediatric Genomics & Systems Medicine InstituteRan2017 to 2050Enrolled100,000ConditionsGenetic Diseases, Genetic SyndromeArmsGenomic sequencing and molecular diagnostic results, if any
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. 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.

Jennifer FriedmanDepartment of Neurosciences, University of California San Diego, San Diego, CA, USA.ORCID 0000-0002-3188-3788
Lynne M BirdDepartment of Pediatrics, University of California San Diego, San Diego, CA, USA.
Richard HaasDepartment of Neurosciences, University of California San Diego, San Diego, CA, USA.
Shira L RobbinsViterbi Family Department of Ophthalmology at the Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA.
Shareef A NahasRady Children's Institute for Genomic Medicine, San Diego, CA, USA.
David P DimmockRady Children's Institute for Genomic Medicine, San Diego, CA, USA.
Matthew J YousefzadehInstitute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
Mariah A WittInstitute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
Laura J NiedernhoferInstitute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
Shimul ChowdhuryRady Children's Institute for Genomic Medicine, San Diego, CA, USA.
Children’s Institute · USUniversity of California San Diego · USUniversity of Minnesota · US

Funding

Targeting Cellular Senescence to Extend HealthspanP01AG062413 · NIA · MAYO CLINIC ROCHESTER · PI Sundeep Khosla, Nathan K LeBrasseur · 2019 to 2026
$28.7M
ConProject-001U19HD077693 · NICHD · RADY PEDIATRIC GENOMICS & SYSTEMS MEDICINE INSTITUTE · PI KINGSMORE, STEPHEN FRANCIS · 2013 to 2018
$6.2M
Measuring nucleotide excision repair in human populationsU01ES029603 · NIEHS · UNIVERSITY OF MINNESOTA · PI NIEDERNHOFER, LAURA JANE · 2018 to 2021
$2.3M
NIA NIH HHS P01 AG062413NICHD NIH HHS U19 HD077693NIEHS NIH HHS U01 ES029603
6 · The paper itself

Abstract

backgroundCockayne syndrome (CS) is a rare autosomal recessive disorder characterized by growth failure and multisystemic degeneration. Excision repair cross-complementation group 6 (ERCC6 OMIM: *609413) is the gene most frequently mutated in CS.

methodsA child with pre and postnatal growth failure and progressive neurologic deterioration with multisystem involvement, and with nondiagnostic whole-exome sequencing, was screened for causal variants with whole-genome sequencing (WGS).

resultsWGS identified biallelic ERCC6 variants, including a previously unreported intronic variant. Pathogenicity of these variants was established by demonstrating reduced levels of ERCC6 mRNA and protein expression, normal unscheduled DNA synthesis, and impaired recovery of RNA synthesis in patient fibroblasts following UV-irradiation.

conclusionThe study confirms the pathogenicity of a previously undescribed upstream intronic variant, highlighting the power of genome sequencing to identify noncoding variants. In addition, this report provides evidence for the utility of a combination approach of genome sequencing plus functional studies to provide diagnosis in a child for whom a lengthy diagnostic odyssey, including exome sequencing, was previously unrevealing.

Indexed as

IntronsCells, CulturedChildCockayne SyndromeDNA HelicasesDNA Repair EnzymesFemaleFibroblastsHumansPoly-ADP-Ribose Binding ProteinsWhole Genome SequencingDNA HelicasesDNA Repair EnzymesERCC6 protein, humanPoly-ADP-Ribose Binding Proteinscockayne syndromeDNA repairERCC6whole-genome sequencing

Identifiers

PMID34076366
PMCPMC8372079
OpenAlexW3164989300

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.