2021
Association of Damaging Variants in Genes With Increased Cancer Risk Among Patients With Congenital Heart Disease
Morton SU, Shimamura A, Newburger PE, Opotowsky AR, Quiat D, Pereira AC, Jin SC, Gurvitz M, Brueckner M, Chung WK, Shen Y, Bernstein D, Gelb BD, Giardini A, Goldmuntz E, Kim RW, Lifton RP, Porter GA, Srivastava D, Tristani-Firouzi M, Newburger JW, Seidman JG, Seidman CE. Association of Damaging Variants in Genes With Increased Cancer Risk Among Patients With Congenital Heart Disease. JAMA Cardiology 2021, 6: 457-462. PMID: 33084842, PMCID: PMC7578917, DOI: 10.1001/jamacardio.2020.4947.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overCase-Control StudiesChildChild, PreschoolFemaleGene Expression RegulationGene FrequencyGenes, NeoplasmGenetic Predisposition to DiseaseGenetic VariationHeart Defects, CongenitalHumansInfantInfant, NewbornLoss of Function MutationMaleMiddle AgedNeoplasmsYoung AdultConceptsCongenital heart diseaseCancer risk genesCancer riskLoF variantsControl participantsHeart diseaseRisk genesMulticenter case-control studyStructural cardiac anomaliesTime of enrollmentCase-control studyDamaging variantsExtracardiac anomaliesExtracardiac manifestationsCardiac anomaliesClinical variablesNeurodevelopmental delayLongitudinal surveillanceMAIN OUTCOMEParent studyCommon birth defectsPatientsEarly interventionFunction variantsMultiple patients
2020
De novo Damaging Variants, Clinical Phenotypes and Post-Operative Outcomes in Congenital Heart Disease
Boskovski MT, Homsy J, Nathan M, Sleeper LA, Morton S, Manheimer KB, Tai A, Gorham J, Lewis M, Swartz M, Alfieris GM, Bacha EA, Karimi M, Meyer D, Nguyen K, Bernstein D, Romano-Adesman A, Porter GA, Goldmuntz E, Chung WK, Srivastava D, Kaltman JR, Tristani-Firouzi M, Lifton R, Roberts AE, Gaynor JW, Gelb BD, Kim R, Seidman JG, Brueckner M, Mayer JE, Newburger JW, Seidman CE. De novo Damaging Variants, Clinical Phenotypes and Post-Operative Outcomes in Congenital Heart Disease. Circulation Genomic And Precision Medicine 2020, 13: e002836-e002836. PMID: 32812804, PMCID: PMC7439931, DOI: 10.1161/circgen.119.002836.Peer-Reviewed Original ResearchConceptsWorse transplant-free survivalTransplant-free survivalExtra-cardiac anomaliesCongenital heart diseaseDe novo variantsHeart diseaseFinal extubationNovo variantsFirst operationPost-operative outcomesOpen heart surgeryPreoperative genetic testingRoutine clinical practiceDamaging variantsWhole-exome sequencingHeart transplantationAdverse outcomesSurgical dataPatientsClinical practiceCardiac repairClinical phenotypeDe novoGenetic testingGenetic abnormalitiesEM-mosaic detects mosaic point mutations that contribute to congenital heart disease
Hsieh A, Morton SU, Willcox JAL, Gorham JM, Tai AC, Qi H, DePalma S, McKean D, Griffin E, Manheimer KB, Bernstein D, Kim RW, Newburger JW, Porter GA, Srivastava D, Tristani-Firouzi M, Brueckner M, Lifton RP, Goldmuntz E, Gelb BD, Chung WK, Seidman CE, Seidman JG, Shen Y. EM-mosaic detects mosaic point mutations that contribute to congenital heart disease. Genome Medicine 2020, 12: 42. PMID: 32349777, PMCID: PMC7189690, DOI: 10.1186/s13073-020-00738-1.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultChildChild, PreschoolHeart Defects, CongenitalHumansInfantMosaicismPoint MutationSoftwareYoung AdultConceptsCongenital heart diseaseHigher allele fractionHeart diseaseCardiac tissueMosaic variantsAllele fractionBlood DNAHigh variant allele fractionSomatic mosaic variantsVariant allele fractionProband-parent triosCardiac malformationsOocyte fertilizationBloodHeart tissueBenign variantsMosaic mutationsExome sequencesTissue DNACardiovascular tissuesGenetic mutationsCHD probandsTrue frequencyCohortTissue
2013
The Congenital Heart Disease Genetic Network Study
Gelb B, Brueckner M, Chung W, Goldmuntz E, Kaltman J, Pablo Kaski J, Kim R, Kline J, Mercer-Rosa L, Porter G, Roberts A, Rosenberg E, Seiden H, Seidman C, Sleeper L, Tennstedt S, Kaltman J, Schramm C, Burns K, Pearson G, Rosenberg E, Newburger J, Breitbart R, Colan S, Geva J, Monafo A, Roberts A, Stryker J, Seidman C, McDonough B, Seidman J, Goldmuntz E, Edman S, Garbarini J, Hakonarson H, Mercer-Rosa L, Mitchell L, Tusi J, White P, Woyciechowski S, Chung W, Warburton D, Awad D, Celia K, Etwaru D, Sond J, Kline J, Korsin R, Lanz A, Marquez E, Williams I, Wilpers A, Yee R, Gelb B, Guevara D, Julian A, Mac Neal M, Mintz C, Peter I, Sachidanandam R, Seiden H, Romano-Adesman A, Gruber D, Stellato N, Brueckner M, Lifton R, Cross N, Deanfield J, Giardini A, Flack K, Porter G, Taillie E, Kim R, Tran N, Tennstedt S, Breitbart R, Dandreo K, Gallagher D, Lu M, Sleeper L, Berlin D, Beiswanger C, Lifton R, Seidman J, Hakonarson H, White P, Italia M, Chung W, Seidman C, Brooks (Chair) M, Olive M, Botkin J, Dupuis J, Garg V, Watson M, Bristow J, Evans T, Kendziorski C, Mardis E, Murray J, Saltz J, Wong H. The Congenital Heart Disease Genetic Network Study. Circulation Research 2013, 112: 698-706. PMID: 23410879, PMCID: PMC3679175, DOI: 10.1161/circresaha.111.300297.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultBiological Specimen BanksChildChild, PreschoolClinical Trials as TopicConfidentialityData CollectionDatabases, FactualDNA Mutational AnalysisFollow-Up StudiesGene DosageGenetic Association StudiesGenomicsGenotypeHeart Defects, CongenitalHospitals, PediatricHumansInfantInfant, NewbornInterdisciplinary CommunicationNational Heart, Lung, and Blood Institute (U.S.)Outcome Assessment, Health CarePatient SelectionPhenotypeProspective StudiesRegistriesSchools, MedicalTranslational Research, BiomedicalUnited StatesYoung AdultConceptsGenetic factorsAtrial septal defectForms of CHDData-coordinating centerLate morbidityMost patientsObstructive lesionsPediatric Cardiac Genomics ConsortiumMedian ageClinical featuresBlood InstituteNational HeartSeptal defectComplex lesionsPremature mortalitySpecific genetic lesionsCore laboratoryCongenital heartCHDSaliva samplesAdequate DNALesionsBirth defectsInfant mortalityProbands
1999
GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart disease
Pehlivan T, Pober B, Brueckner M, Garrett S, Slaugh R, Van Rheeden R, Wilson D, Watson M, Hing A. GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart disease. American Journal Of Medical Genetics 1999, 83: 201-206. PMID: 10096597, DOI: 10.1002/(sici)1096-8628(19990319)83:3<201::aid-ajmg11>3.0.co;2-v.Peer-Reviewed Original ResearchConceptsCardiac transcription factor genesZinc finger transcription factorHuman chromosome armsTranscription factor genesFinger transcription factorCardiac gene expressionChromosome armsTranscription factorsFactor genesGene expressionGATA4 geneInterstitial deletionGATA-4GenesLociFISH analysisSitu hybridizationDeletionHaploinsufficiencySubmicroscopic deletionRecent studiesPhenotype of patientsCellsMonosomyNormal karyotype