Evidence map›Paper›PMID 37165897›Full record

ArticleCirculation. Genomic and precision medicine2023

Contribution of Previously Unrecognized RNA Splice-Altering Variants to Congenital Heart Disease.

Min Young Jang, Parth N Patel, Alexandre C Pereira, Jon A L Willcox, Alireza Haghighi, Angela C Tai, Kaoru Ito, Sarah U Morton, Joshua M Gorham, David M McKean and 16 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Genomic and precision medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01196182 (Congenital Heart Disease GEnetic NEtwork Study), which is not on this map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.3field-weighted citation impact, top 12% 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.

NCT01196182 active not recruitingnot on this map

Congenital Heart Disease GEnetic NEtwork Study (CHD GENES)

TypeobservationalSponsorChildren's Hospital Medical Center, CincinnatiRan2010 to 2032Enrolled32,000ConditionsCongenital Heart Defects
3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
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  10. Discovery and functional investigation ofAmerican journal of translational research · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 15 institutions in 3 countries.

Min Young JangDepartments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.
Parth N PatelDepartments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.ORCID 0000-0003-3561-796X
Alexandre C PereiraDepartments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.
Jon A L WillcoxDepartments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.
Alireza HaghighiDepartments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.ORCID 0000-0003-0683-4922
Angela C TaiDepartments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.
Kaoru ItoLaboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan (K.I.).ORCID 0000-0003-1843-773X
Sarah U MortonDepartments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.
Joshua M GorhamDepartments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.
David M McKeanDepartments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.
Steven R DePalmaDepartments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.
Daniel BernsteinDepartment of Pediatrics, Stanford University, Palo Alto, CA (D.B.).ORCID 0000-0001-7761-5853
Martina BruecknerDepartments of Genetics (M.B.), Yale University School of Medicine, New Haven, CT.
Wendy K ChungDepartments of Pediatrics (W.K.C.), Columbia University Medical Center, New York, NY.ORCID 0000-0003-3438-5685
Alessandro GiardiniCardiorespiratory Unit, Great Ormond Street Hospital, London, United Kingdom (A.G.).
Elizabeth GoldmuntzDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (E.G.).ORCID 0000-0003-2936-4396
Jonathan R KaltmanHeart Development and Structural Diseases Branch, Division of Cardiovascular Sciences, National Institute of Heart, Lung, and Blood, National Institutes of Health, Bethesda, MD (J.R.K.).
Richard KimDepartment of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (R.K.).ORCID 0000-0003-3326-6916
Jane W NewburgerDepartment of Cardiology (J.W.N.), Boston Children's Hospital, MA.ORCID 0000-0002-7794-9017
Yufeng ShenSystems Biology (Y.S.), Columbia University Medical Center, New York, NY.ORCID 0000-0002-1299-5979
Deepak SrivastavaGladstone Institute of Cardiovascular Disease, San Francisco, CA (D.S.).ORCID 0000-0002-3480-5953
Martin Tristani-FirouziNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT (M.T.-F.).ORCID 0000-0001-5916-442X
Bruce D GelbMindich Child Health and Development Institute (B.D.G.), Icahn School of Medicine at Mount Sinai, New York.ORCID 0000-0001-8527-5027
George A PorterDepartment of Pediatrics, University of Rochester Medical Center, NY (G.A.P.).ORCID 0000-0003-0726-9988
Christine E Seidman *Departments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.
Jonathan G Seidman *Departments of Genetics (M.Y.J., P.N.P., A.C.P., J.A.L.W., A.H., A.C.T., S.U.M., J.M.G., D.M.M., S.R.D., C.E.S., J.G.S.), Harvard Medical School, Boston, MA.ORCID 0000-0002-9082-3566
MACOM (United States) · USBrigham and Women's Hospital · USColumbia University Irving Medical Center · USBoston Children's Hospital · USCedars-Sinai Smidt Heart Institute · USChild Health and Development Institute · USGladstone Institutes · USGreat Ormond Street Hospital · GBNational Heart Lung and Blood Institute · USPalo Alto University · USRIKEN Center for Integrative Medical Sciences · JPUniversity of Pennsylvania · USUniversity of Rochester Medical Center · USUniversity of Utah · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Genomic Effects on Right Ventricular Function, Clinical Features and Outcomes in CHDU01HL098147 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI NEWBURGER, JANE W., ROBERTS, AMY E · 2009 to 2024
$6.7M
Genetic determinants of human heterotaxy and aortic arch malformationU01HL098162 · NHLBI · YALE UNIVERSITY · PI BRUECKNER, MARTINA, GRUBER, PETER J · 2009 to 2024
$5.9M
The Genomic Basis of Congenital Heart Disease and Neurodevelopmental OutcomesUM1HL098147 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI NEWBURGER, JANE W., ROBERTS, AMY E · 2015 to 2019
$2.4M
Integration of RNA and Genome Sequences to Identify Genetic Risk in Hypoplastic Left Heart SyndromeK08HL157653 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Sarah Uhler Morton · 2022 to 2026
$840k
Discovery of Novel Genetic Variants Underlying Unexplained Hypertrophic Cardiomyopathy by Whole Genome Sequencing, RNA-seq and iPSC modelingK08HL150284 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI HAGHIGHI, ALIREZA · 2020 to 2024
$832k
Computational Prioritization of Coding and Non-Coding Variants in Congenital Heart DiseaseR03HL150412 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI MORTON, SARAH, SEIDMAN, JONATHAN G · 2021 to 2022
$371k
NCATS NIH HHS UL1 TR001863NHLBI NIH HHS K08 HL150284NHLBI NIH HHS K08 HL157653NHLBI NIH HHS R03 HL150412NHLBI NIH HHS U01 HL098147NHLBI NIH HHS U01 HL098162NHLBI NIH HHS UM1 HL098147
6 · The paper itself

Abstract

backgroundKnown genetic causes of congenital heart disease (CHD) explain <40% of CHD cases, and interpreting the clinical significance of variants with uncertain functional impact remains challenging. We aim to improve diagnostic classification of variants in patients with CHD by assessing the impact of noncanonical splice region variants on RNA splicing.

methodsWe tested de novo variants from trio studies of 2649 CHD probands and their parents, as well as rare (allele frequency, <2×10

resultsWe identified 53 de novo and 74 rare variants in CHD cases that alter splicing and thus are loss of function. Of these, 77 variants are in known dominant, recessive, and candidate CHD genes, including

conclusionsThrough assessment of RNA splicing, we identified a new loss-of-function variant within a CHD gene in 78 probands, of whom 69 (1.5%; n=4472) did not have a previously established genetic explanation for CHD. Identification of splice-altering variants improves diagnostic classification and genetic diagnoses for CHD. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT01196182.

Indexed as

Heart Defects, CongenitalRNAChildGene FrequencyHumansMutationRepressor ProteinsRNA SplicingRNA Splicing FactorsRBFOX2 protein, humanRepressor ProteinsRNARNA Splicing FactorsalgorithmsalleleschildhumansRNA splicing

Identifiers

PMID37165897
PMCPMC10404383
OpenAlexW4376131349

What OpenQuestion holds

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LicenceCC BY
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.