Evidence map›Paper›PMID 22700954›Full record

ArticleScience translational medicine2012

Exome sequencing can improve diagnosis and alter patient management.

Tracy J Dixon-Salazar, Jennifer L Silhavy, Nitin Udpa, Jana Schroth, Stephanie Bielas, Ashleigh E Schaffer, Jesus Olvera, Vineet Bafna, Maha S Zaki, Ghada H Abdel-Salam and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed, 3 pooled it
20.9field-weighted citation impact, top 1% 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

153 citing papers in PubMed, 3 syntheses or guidelines pooled it, 257 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Mastering genetics for your clinic: A step-by-step guide.The Journal of allergy and clinical immunology · 2025
    Review
  7. Article
  8. Review
  9. Review
  10. Regulation of yeast polarized exocytosis by phosphoinositide lipids.Cellular and molecular life sciences : CMLS · 2024
    Review
  11. Decoding the genetic landscape of autism: A comprehensive review.World journal of clinical pediatrics · 2024
    Article
  12. Article
  13. A clinical approach to diagnosis and management of mitochondrial myopathies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024
    Review
  14. Review
  15. Article
  16. Article
  17. Ciliogenesis membrane dynamics and organization.Seminars in cell & developmental biology · 2023
    Review
  18. Article
  19. Review
  20. Review

93 more citing papers are in PubMed but not listed here.

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

29 authors at 4 institutions in 3 countries.

Tracy J Dixon-SalazarHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Jennifer L SilhavyHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Nitin UdpaDepartment of Computer Sciences, School of Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
Jana SchrothHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Stephanie BielasHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Ashleigh E SchafferHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Jesus OlveraHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Vineet BafnaDepartment of Computer Sciences, School of Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
Maha S ZakiClinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo 12311, Egypt.
Ghada H Abdel-SalamClinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo 12311, Egypt.
Lobna A MansourCairo University Children's Hospital, Cairo 406, Egypt.
Laila SelimCairo University Children's Hospital, Cairo 406, Egypt.
Sawsan Abdel-HadiCairo University Children's Hospital, Cairo 406, Egypt.
Naima MarzoukiLaboratoire Génétique Moléculaire, El Razi University Hospital, Marrakech 2360, Morocco.
Tawfeg Ben-OmranClinical and Metabolic Genetics Division, Department of Pediatrics, Hamad Medical Corporation, Doha 3050, Qatar.
Nouriya A Al-SaanaDepartment of Pediatrics, Dhahran Health Center, Saudi Aramco Corporation, Dhahran 31311, KSA.
F Müjgan SonmezChild Neurology Department, Medical School of Karadeniz Technical University, Trabzon 61080, Turkey.
Figen CelepMedical Biology Department, Medical School of Karadeniz Technical University, Trabzon 61080, Turkey.
Matloob AzamDepartment of Paediatrics and Child Neurology, Wah Medical College, Wah Cantt, Pakistan.
Kiley J HillHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Adrienne CollazoHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Ali G FenstermakerHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Gaia NovarinoHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Naiara AkizuHoward Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Kiran V GarimellaThe Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Carrie SougnezThe Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Carsten RussThe Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Stacey B Gabriel *The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Joseph G Gleeson *Howard Hughes Medical Institute, Institute for Genomic Medicine, Rady Children's Hospital, University of California, San Diego, San Diego, CA 92093, USA.
Massachusetts Institute of Technology · USNational Research Centre · EGBroad Institute · USHamad Medical Corporation · QA

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Project 3. Genetic Models of Human Structural Brain Defects in ZebrafishP01HD070494 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2011 to 2016
$6.7M
Molecular Characterization of Joubert SyndromeR01NS048453 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2004 to 2020
$6.0M
Doublecortin In Neuronal MigrationR01NS041537 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2002 to 2014
$3.9M
Jouberin and Nephrocystin in Joubert SyndromeR01NS052455 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2007 to 2015
$3.0M
GENOTYPING FOR LOCATING HUMAN DISEASE GENESN01HG065403 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID L · 1996 to 2000
$1.7M
Howard Hughes Medical InstituteNHGRI NIH HHS N01 HG065403NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54HG003067NICHD NIH HHS P01 HD070494NICHD NIH HHS P01HD070494NINDS NIH HHS R01 NS041537NINDS NIH HHS R01NS041537NINDS NIH HHS R01 NS048453NINDS NIH HHS R01NS048453NINDS NIH HHS R01 NS052455NINDS NIH HHS R01NS052455
6 · The paper itself

Abstract

The translation of "next-generation" sequencing directly to the clinic is still being assessed but has the potential for genetic diseases to reduce costs, advance accuracy, and point to unsuspected yet treatable conditions. To study its capability in the clinic, we performed whole-exome sequencing in 118 probands with a diagnosis of a pediatric-onset neurodevelopmental disease in which most known causes had been excluded. Twenty-two genes not previously identified as disease-causing were identified in this study (19% of cohort), further establishing exome sequencing as a useful tool for gene discovery. New genes identified included EXOC8 in Joubert syndrome and GFM2 in a patient with microcephaly, simplified gyral pattern, and insulin-dependent diabetes. Exome sequencing uncovered 10 probands (8% of cohort) with mutations in genes known to cause a disease different from the initial diagnosis. Upon further medical evaluation, these mutations were found to account for each proband's disease, leading to a change in diagnosis, some of which led to changes in patient management. Our data provide proof of principle that genomic strategies are useful in clarifying diagnosis in a proportion of patients with neurodevelopmental disorders.

Indexed as

ExomeFemaleHumansMaleMutationPedigreeSequence Analysis, DNAVesicular Transport ProteinsEXOC8 protein, humanVesicular Transport Proteins

Identifiers

PMID22700954
PMCPMC4442637
OpenAlexW1966045237

What OpenQuestion 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 OpenQuestion graph.