2023
SMC5 Plays Independent Roles in Congenital Heart Disease and Neurodevelopmental Disability
O'Brien M, Pryzhkova M, Lake E, Mandino F, Shen X, Karnik R, Atkins A, Xu M, Ji W, Konstantino M, Brueckner M, Ment L, Khokha M, Jordan P. SMC5 Plays Independent Roles in Congenital Heart Disease and Neurodevelopmental Disability. International Journal Of Molecular Sciences 2023, 25: 430. PMID: 38203602, PMCID: PMC10779392, DOI: 10.3390/ijms25010430.Peer-Reviewed Original ResearchThe H2Bub1-deposition complex is required for human and mouse cardiogenesis
Barish S, Berg K, Drozd J, Berglund-Brown I, Khizir L, Wasson L, Seidman C, Seidman J, Chen S, Brueckner M. The H2Bub1-deposition complex is required for human and mouse cardiogenesis. Development 2023, 150: dev201899. PMID: 38038666, PMCID: PMC10730087, DOI: 10.1242/dev.201899.Peer-Reviewed Original ResearchEpithelial-Mesenchymal Cross-Talks in Murine Models of Renal Ciliopathy
Sun Z, Hsieh C, Li Y, Xu W, Makova S, Brueckner M. Epithelial-Mesenchymal Cross-Talks in Murine Models of Renal Ciliopathy. Journal Of The American Society Of Nephrology 2023, 34: 563-563. DOI: 10.1681/asn.20233411s1563a.Peer-Reviewed Original ResearchSingle-cell reconstruction and mutation enrichment analysis identifies dysregulated cardiomyocyte and endothelial cells in congenital heart disease
Tambi R, Zehra B, Nandkishore S, Sharafat S, Kader F, Nassir N, Mohamed N, Ahmed A, Abdel Hameid R, Alasrawi S, Brueckner M, Kuebler W, Chung W, Alsheikh-Ali A, Di Donato R, Uddin M, Berdiev B. Single-cell reconstruction and mutation enrichment analysis identifies dysregulated cardiomyocyte and endothelial cells in congenital heart disease. Physiological Genomics 2023, 55: 634-646. PMID: 37811720, PMCID: PMC11550899, DOI: 10.1152/physiolgenomics.00070.2023.Peer-Reviewed Original ResearchConceptsSingle-cell transcriptomesCHD genesRisk genesEndocardial cellsMultiple genesCell typesSingle-cell transcriptomicsPhenotypic heterogeneityDe novo variantsCongential heart diseaseSingle-cell reconstructionGenesReconstruction analysisNeonatal congenital anomaliesGene heterogeneityAnalysis identifiesTranscriptomeMissense variantsNovo variantsCongenital heart diseaseGenomicsHeterogenous expressionFunction variantsHeart diseaseGenetics guidelinesInactivation of Invs/Nphp2 in renal epithelial cells drives infantile nephronophthisis like phenotypes in mouse
Li Y, Xu W, Makova S, Brueckner M, Sun Z. Inactivation of Invs/Nphp2 in renal epithelial cells drives infantile nephronophthisis like phenotypes in mouse. ELife 2023, 12: e82395. PMID: 36920028, PMCID: PMC10154023, DOI: 10.7554/elife.82395.Peer-Reviewed Original ResearchConceptsFlox/Valproic acidRenal fibrosisCyst formationEnd-stage renal diseaseMutant miceHistone deacetylase inhibitor valproic acidKidney function declineStage renal diseaseCell proliferationInhibitor valproic acidEpithelial-stromal crosstalkKnockout mouse modelRenal cyst formationCyst burdenRenal diseaseFunction declineInterstitial fibrosisDisease progressionStromal fibrosisTargeted therapyInfantile nephronophthisisMouse modelMyofibroblast activationRenal epithelial cellsAssociation of Predicted Damaging De Novo Variants on Ventricular Function in Individuals With Congenital Heart Disease
Lewis M, Hsieh A, Qiao L, Tan R, Kazzi B, Channing A, Griffin E, Jobanputra V, Su J, Shahryar C, Kochilas L, Gaynor J, Lee T, Goldmuntz E, Russell M, Mital S, Tristani M, Brueckner M, Newburger J, Shen Y, Chung W. Association of Predicted Damaging De Novo Variants on Ventricular Function in Individuals With Congenital Heart Disease. Circulation Genomic And Precision Medicine 2023, 16: e003900. PMID: 36866680, PMCID: PMC10121832, DOI: 10.1161/circgen.122.003900.Peer-Reviewed Original ResearchCilia function as calcium-mediated mechanosensors that instruct left-right asymmetry
Djenoune L, Mahamdeh M, Truong T, Nguyen C, Fraser S, Brueckner M, Howard J, Yuan S. Cilia function as calcium-mediated mechanosensors that instruct left-right asymmetry. Science 2023, 379: 71-78. PMID: 36603098, PMCID: PMC9939240, DOI: 10.1126/science.abq7317.Peer-Reviewed Original ResearchAssociation of Potentially Damaging De Novo Gene Variants With Neurologic Outcomes in Congenital Heart Disease
Morton S, Norris-Brilliant A, Cunningham S, King E, Goldmuntz E, Brueckner M, Miller T, Thomas N, Liu C, Adams H, Bellinger D, Cleveland J, Cnota J, Dale A, Frommelt M, Gelb B, Grant P, Goldberg C, Huang H, Kuperman J, Li J, McQuillen P, Panigrahy A, Porter G, Roberts A, Russell M, Seidman C, Tivarus M, Anagnoustou E, Hagler D, Chung W, Newburger J. Association of Potentially Damaging De Novo Gene Variants With Neurologic Outcomes in Congenital Heart Disease. JAMA Network Open 2023, 6: e2253191. PMID: 36701153, PMCID: PMC9880793, DOI: 10.1001/jamanetworkopen.2022.53191.Peer-Reviewed Original Research
2022
Network assisted analysis of de novo variants using protein-protein interaction information identified 46 candidate genes for congenital heart disease
Xie Y, Jiang W, Dong W, Li H, Jin SC, Brueckner M, Zhao H. Network assisted analysis of de novo variants using protein-protein interaction information identified 46 candidate genes for congenital heart disease. PLOS Genetics 2022, 18: e1010252. PMID: 35671298, PMCID: PMC9205499, DOI: 10.1371/journal.pgen.1010252.Peer-Reviewed Original ResearchQuantifying concordant genetic effects of de novo mutations on multiple disorders
Guo H, Hou L, Shi Y, Jin SC, Zeng X, Li B, Lifton R, Brueckner M, Zhao H, Lu Q. Quantifying concordant genetic effects of de novo mutations on multiple disorders. ELife 2022, 11: e75551. PMID: 35666111, PMCID: PMC9217133, DOI: 10.7554/elife.75551.Peer-Reviewed Original ResearchMutation spectrum of congenital heart disease in a consanguineous Turkish population
Dong W, Kaymakcalan H, Jin SC, Diab NS, Tanıdır C, Yalcin ASY, Ercan‐Sencicek A, Mane S, Gunel M, Lifton RP, Bilguvar K, Brueckner M. Mutation spectrum of congenital heart disease in a consanguineous Turkish population. Molecular Genetics & Genomic Medicine 2022, 10: e1944. PMID: 35481623, PMCID: PMC9184665, DOI: 10.1002/mgg3.1944.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingLaterality defectsUnique genetic architectureCongenital heart diseaseConsanguineous familyGenetic architectureCausal genesCHD genesGenome analysisHomozygous variantGenetic landscapeGenetic lesionsGenomic alterationsHeart diseaseConsanguineous populationFunction variantsRecessive variantsCHD probandsGenesType of CHDMutation spectrumStructural congenital heart diseaseVariantsCHD subjectsAdditional patientsNeither cardiac mitochondrial DNA variation nor copy number contribute to congenital heart disease risk
Willcox JAL, Geiger JT, Morton SU, McKean D, Quiat D, Gorham JM, Tai AC, DePalma S, Bernstein D, Brueckner M, Chung WK, Giardini A, Goldmuntz E, Kaltman JR, Kim R, Newburger JW, Shen Y, Srivastava D, Tristani-Firouzi M, Gelb B, Porter GA, Seidman JG, Seidman CE. Neither cardiac mitochondrial DNA variation nor copy number contribute to congenital heart disease risk. American Journal Of Human Genetics 2022, 109: 961-966. PMID: 35397206, PMCID: PMC9118105, DOI: 10.1016/j.ajhg.2022.03.011.Peer-Reviewed Original ResearchGenome-Wide De Novo Variants in Congenital Heart Disease Are Not Associated With Maternal Diabetes or Obesity
Morton SU, Pereira AC, Quiat D, Richter F, Kitaygorodsky A, Hagen J, Bernstein D, Brueckner M, Goldmuntz E, Kim RW, Lifton RP, Porter GA, Tristani-Firouzi M, Chung WK, Roberts A, Gelb BD, Shen Y, Newburger JW, Seidman JG, Seidman CE. Genome-Wide De Novo Variants in Congenital Heart Disease Are Not Associated With Maternal Diabetes or Obesity. Circulation Genomic And Precision Medicine 2022, 15: e003500. PMID: 35130025, PMCID: PMC9295870, DOI: 10.1161/circgen.121.003500.Peer-Reviewed Original ResearchConceptsCongenital heart diseaseDamaging de novo variantsMaternal diabetesPrenatal exposureHeart diseaseDe novo variantsParental ageIncidence of CHDNovo variantsCauses of CHDMaternal obesityObese mothersDiabetes riskPatientsCommon anomalyObesityDiabetesAgeWhole-genome sequencingDiseaseMothersGene studiesCauseExposureInfants
2021
A change of heart: new roles for cilia in cardiac development and disease
Djenoune L, Berg K, Brueckner M, Yuan S. A change of heart: new roles for cilia in cardiac development and disease. Nature Reviews Cardiology 2021, 19: 211-227. PMID: 34862511, PMCID: PMC10161238, DOI: 10.1038/s41569-021-00635-z.Peer-Reviewed Original ResearchConceptsCongenital heart diseaseHeart diseaseCardiac valve disordersAortic valve diseaseMitral valve prolapseCardiac developmentValve diseaseValve prolapseMyocardial fibrosisValve disordersCardiac abnormalitiesPresence of ciliaCardiac fibroblastsCilia functionContractile forceDiseaseFunction contributesLines of evidenceDefective primary ciliaPotential roleHeart regenerationBroader roleHeartDisordersLatest findingsMolecular Genetics and Complex Inheritance of Congenital Heart Disease
Diab NS, Barish S, Dong W, Zhao S, Allington G, Yu X, Kahle KT, Brueckner M, Jin SC. Molecular Genetics and Complex Inheritance of Congenital Heart Disease. Genes 2021, 12: 1020. PMID: 34209044, PMCID: PMC8307500, DOI: 10.3390/genes12071020.Peer-Reviewed Original ResearchConceptsHigh-throughput genomic technologiesHigh-throughput sequencingGenetic architectureCHD familyGenetic variationSophisticated analysis strategiesCilia genesComplex inheritancePathway genesDe novo mutationsGenomic technologiesCauses of CHDMolecular geneticsBiological pathwaysMolecular diagnosisNumber variationsVEGF pathway genesGenesChromatinMutationsNovo mutationsGenetic etiologyTransmitted mutationsGenetic explanationSequencingIntegrative modeling of transmitted and de novo variants identifies novel risk genes for congenital heart disease
Li M, Zeng X, Jin C, Jin SC, Dong W, Brueckner M, Lifton R, Lu Q, Zhao H. Integrative modeling of transmitted and de novo variants identifies novel risk genes for congenital heart disease. Quantitative Biology 2021, 9: 216-227. PMID: 35414959, PMCID: PMC9000521, DOI: 10.15302/j-qb-021-0248.Peer-Reviewed Original ResearchAssociation 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 patientsMechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency
Ward T, Tai W, Morton S, Impens F, Van Damme P, Van Haver D, Timmerman E, Venturini G, Zhang K, Jang MY, Willcox JAL, Haghighi A, Gelb BD, Chung WK, Goldmuntz E, Porter GA, Lifton R, Brueckner M, Yost HJ, Bruneau BG, Gorham J, Kim Y, Pereira A, Homsy J, Benson CC, DePalma SR, Varland S, Chen CS, Arnesen T, Gevaert K, Seidman C, Seidman JG. Mechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency. Circulation Research 2021, 128: 1156-1169. PMID: 33557580, PMCID: PMC8048381, DOI: 10.1161/circresaha.120.316966.Peer-Reviewed Original Research
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 abnormalitiesGenomic analyses implicate noncoding de novo variants in congenital heart disease
Richter F, Morton SU, Kim SW, Kitaygorodsky A, Wasson LK, Chen KM, Zhou J, Qi H, Patel N, DePalma SR, Parfenov M, Homsy J, Gorham JM, Manheimer KB, Velinder M, Farrell A, Marth G, Schadt EE, Kaltman JR, Newburger JW, Giardini A, Goldmuntz E, Brueckner M, Kim R, Porter GA, Bernstein D, Chung WK, Srivastava D, Tristani-Firouzi M, Troyanskaya OG, Dickel DE, Shen Y, Seidman JG, Seidman CE, Gelb BD. Genomic analyses implicate noncoding de novo variants in congenital heart disease. Nature Genetics 2020, 52: 769-777. PMID: 32601476, PMCID: PMC7415662, DOI: 10.1038/s41588-020-0652-z.Peer-Reviewed Original Research