Evidence map›Paper›PMID 27418595›Full record

ArticleCirculation. Cardiovascular genetics2016

Utilization of Whole Exome Sequencing to Identify Causative Mutations in Familial Congenital Heart Disease.

Stephanie LaHaye, Don Corsmeier, Madhumita Basu, Jessica L Bowman, Sara Fitzgerald-Butt, Gloria Zender, Kevin Bosse, Kim L McBride, Peter White, Vidu Garg

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

Article in Circulation. Cardiovascular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01192048 (Genetic Testing of Individuals and Families With Congenital Heart Disease), which is not on this map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% 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.

NCT01192048 recruitingnot on this map

Genetic Testing of Individuals and Families With Congenital Heart Disease

TypeobservationalSponsorNationwide Children's HospitalRan2009 to 2030Enrolled5,000ConditionsCongenital Heart DiseaseArmsBlood Sample Collection
3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Pooled it
  2. Genetics of Congenital Heart Disease.Clinics in perinatology · 2025
    Review
  3. Review
  4. Genetic and Environmental Contributors To Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2025
    Review
  5. The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024
    Review
  6. Review
  7. In-Depth Genomic Analysis: The New Challenge in Congenital Heart Disease.International journal of molecular sciences · 2024
    Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2022
    Article
  16. Molecular genetic mechanisms of congenital heart disease.Current opinion in genetics & development · 2022
    Review
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Stephanie LaHayeFrom the Center for Cardiovascular Research, The Research Institute (S.L., M.B., S.F.-B., G.Z., K.B., K.L.M., V.G.), The Heart Center (S.L., M.B., J.L.B., S.F.-B., K.L.M., V.G.), and Biomedical Genomics Core and the Center for Microbial Pathogenesis, The Research Institute (D.C., P.W.), Nationwide Children's Hospital, Columbus, OH; and Department of Molecular Genetics (S.L., V.G.) and Department of Pediatrics (J.L.B., S.F.-B., K.L.M., P.W., V.G.), The Ohio State University, Columbus.
Don CorsmeierFrom the Center for Cardiovascular Research, The Research Institute (S.L., M.B., S.F.-B., G.Z., K.B., K.L.M., V.G.), The Heart Center (S.L., M.B., J.L.B., S.F.-B., K.L.M., V.G.), and Biomedical Genomics Core and the Center for Microbial Pathogenesis, The Research Institute (D.C., P.W.), Nationwide Children's Hospital, Columbus, OH; and Department of Molecular Genetics (S.L., V.G.) and Department of Pediatrics (J.L.B., S.F.-B., K.L.M., P.W., V.G.), The Ohio State University, Columbus.
Madhumita BasuFrom the Center for Cardiovascular Research, The Research Institute (S.L., M.B., S.F.-B., G.Z., K.B., K.L.M., V.G.), The Heart Center (S.L., M.B., J.L.B., S.F.-B., K.L.M., V.G.), and Biomedical Genomics Core and the Center for Microbial Pathogenesis, The Research Institute (D.C., P.W.), Nationwide Children's Hospital, Columbus, OH; and Department of Molecular Genetics (S.L., V.G.) and Department of Pediatrics (J.L.B., S.F.-B., K.L.M., P.W., V.G.), The Ohio State University, Columbus.
Jessica L BowmanFrom the Center for Cardiovascular Research, The Research Institute (S.L., M.B., S.F.-B., G.Z., K.B., K.L.M., V.G.), The Heart Center (S.L., M.B., J.L.B., S.F.-B., K.L.M., V.G.), and Biomedical Genomics Core and the Center for Microbial Pathogenesis, The Research Institute (D.C., P.W.), Nationwide Children's Hospital, Columbus, OH; and Department of Molecular Genetics (S.L., V.G.) and Department of Pediatrics (J.L.B., S.F.-B., K.L.M., P.W., V.G.), The Ohio State University, Columbus.
Sara Fitzgerald-ButtFrom the Center for Cardiovascular Research, The Research Institute (S.L., M.B., S.F.-B., G.Z., K.B., K.L.M., V.G.), The Heart Center (S.L., M.B., J.L.B., S.F.-B., K.L.M., V.G.), and Biomedical Genomics Core and the Center for Microbial Pathogenesis, The Research Institute (D.C., P.W.), Nationwide Children's Hospital, Columbus, OH; and Department of Molecular Genetics (S.L., V.G.) and Department of Pediatrics (J.L.B., S.F.-B., K.L.M., P.W., V.G.), The Ohio State University, Columbus.
Gloria ZenderFrom the Center for Cardiovascular Research, The Research Institute (S.L., M.B., S.F.-B., G.Z., K.B., K.L.M., V.G.), The Heart Center (S.L., M.B., J.L.B., S.F.-B., K.L.M., V.G.), and Biomedical Genomics Core and the Center for Microbial Pathogenesis, The Research Institute (D.C., P.W.), Nationwide Children's Hospital, Columbus, OH; and Department of Molecular Genetics (S.L., V.G.) and Department of Pediatrics (J.L.B., S.F.-B., K.L.M., P.W., V.G.), The Ohio State University, Columbus.
Kevin BosseFrom the Center for Cardiovascular Research, The Research Institute (S.L., M.B., S.F.-B., G.Z., K.B., K.L.M., V.G.), The Heart Center (S.L., M.B., J.L.B., S.F.-B., K.L.M., V.G.), and Biomedical Genomics Core and the Center for Microbial Pathogenesis, The Research Institute (D.C., P.W.), Nationwide Children's Hospital, Columbus, OH; and Department of Molecular Genetics (S.L., V.G.) and Department of Pediatrics (J.L.B., S.F.-B., K.L.M., P.W., V.G.), The Ohio State University, Columbus.
Kim L McBrideFrom the Center for Cardiovascular Research, The Research Institute (S.L., M.B., S.F.-B., G.Z., K.B., K.L.M., V.G.), The Heart Center (S.L., M.B., J.L.B., S.F.-B., K.L.M., V.G.), and Biomedical Genomics Core and the Center for Microbial Pathogenesis, The Research Institute (D.C., P.W.), Nationwide Children's Hospital, Columbus, OH; and Department of Molecular Genetics (S.L., V.G.) and Department of Pediatrics (J.L.B., S.F.-B., K.L.M., P.W., V.G.), The Ohio State University, Columbus.
Peter WhiteFrom the Center for Cardiovascular Research, The Research Institute (S.L., M.B., S.F.-B., G.Z., K.B., K.L.M., V.G.), The Heart Center (S.L., M.B., J.L.B., S.F.-B., K.L.M., V.G.), and Biomedical Genomics Core and the Center for Microbial Pathogenesis, The Research Institute (D.C., P.W.), Nationwide Children's Hospital, Columbus, OH; and Department of Molecular Genetics (S.L., V.G.) and Department of Pediatrics (J.L.B., S.F.-B., K.L.M., P.W., V.G.), The Ohio State University, Columbus. Peter.White@nationwidechildrens.org Vidu.Garg@nationwidechildrens.org.
Vidu GargFrom the Center for Cardiovascular Research, The Research Institute (S.L., M.B., S.F.-B., G.Z., K.B., K.L.M., V.G.), The Heart Center (S.L., M.B., J.L.B., S.F.-B., K.L.M., V.G.), and Biomedical Genomics Core and the Center for Microbial Pathogenesis, The Research Institute (D.C., P.W.), Nationwide Children's Hospital, Columbus, OH; and Department of Molecular Genetics (S.L., V.G.) and Department of Pediatrics (J.L.B., S.F.-B., K.L.M., P.W., V.G.), The Ohio State University, Columbus. Peter.White@nationwidechildrens.org Vidu.Garg@nationwidechildrens.org.
Nationwide Children's Hospital · US

Funding

Exome sequencing and functional studies in familial CHDR01HL109758 · NHLBI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI GARG, VIDU, MCBRIDE, KIM LEWIS · 2012 to 2015
$2.7M
Training in Congenital and Acquired Heart DiseaseT32HL098039 · NHLBI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI GARG, VIDU, MOHLER, PETER J. · 2009 to 2019
$2.5M
NHLBI NIH HHS R01 HL109758NHLBI NIH HHS T32 HL098039
6 · The paper itself

Abstract

backgroundCongenital heart disease (CHD) is the most common type of birth defect with family- and population-based studies supporting a strong genetic cause for CHD. The goal of this study was to determine whether a whole exome sequencing (WES) approach could identify pathogenic-segregating variants in multiplex CHD families. METHODS AND

resultsWES was performed on 9 kindreds with familial CHD, 4 with atrial septal defects, 2 with patent ductus arteriosus, 2 with tetralogy of Fallot, and 1 with pulmonary valve dysplasia. Rare variants (<1% minor allele frequency) that segregated with disease were identified by WES, and variants in 69 CHD candidate genes were further analyzed. These selected variants were subjected to in silico analysis to predict pathogenicity and resulted in the discovery of likely pathogenic mutations in 3 of 9 (33%) families. A GATA4 mutation in the transactivation domain, p.G115W, was identified in familial atrial septal defects and demonstrated decreased transactivation ability in vitro. A p.I263V mutation in TLL1 was identified in an atrial septal defects kindred and is predicted to affect the enzymatic functionality of TLL1. A disease-segregating splice donor site mutation in MYH11 (c.4599+1delG) was identified in familial patent ductus arteriosus and found to disrupt normal splicing of MYH11 mRNA in the affected individual.

conclusionsOur findings demonstrate the clinical utility of WES to identify causative mutations in familial CHD and demonstrate the successful use of a CHD candidate gene list to allow for a more streamlined approach enabling rapid prioritization and identification of likely pathogenic variants from large WES data sets. CLINICAL

trial registrationURL: https://clinicaltrials.gov; Unique Identifier: NCT0112048.

Indexed as

ExomeMutationAdolescentCells, CulturedChildChild, PreschoolComputer SimulationDatabases, GeneticDNA Mutational AnalysisDuctus Arteriosus, PatentFemaleGATA4 Transcription FactorGene FrequencyGenetic MarkersGenetic Predisposition to DiseaseGenome-Wide Association StudyGATA4 protein, humanGATA4 Transcription FactorGenetic MarkersMYH11 protein, humanMyosin Heavy ChainsTLL1 protein, humanTolloid-Like Metalloproteinasesductus arteriosus, patentexomegenetic testingheart septal defects, atrialtetralogy of Fallot

Identifiers

PMID27418595
PMCPMC5412122
OpenAlexW2469450953

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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.