2023
Single-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 guidelines
2022
Mutation 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 patients
2020
De novo damaging variants associated with congenital heart diseases contribute to the connectome
Ji W, Ferdman D, Copel J, Scheinost D, Shabanova V, Brueckner M, Khokha MK, Ment LR. De novo damaging variants associated with congenital heart diseases contribute to the connectome. Scientific Reports 2020, 10: 7046. PMID: 32341405, PMCID: PMC7184603, DOI: 10.1038/s41598-020-63928-2.Peer-Reviewed Original ResearchMeSH KeywordsConnectomeDNA HelicasesDNA-Binding ProteinsExomeFemaleHeart Defects, CongenitalHistone-Lysine N-MethyltransferaseHomeodomain ProteinsHumansMaleMi-2 Nucleosome Remodeling and Deacetylase ComplexMutationMutation, MissenseMyeloid-Lymphoid Leukemia ProteinNerve Tissue ProteinsProtein Tyrosine Phosphatase, Non-Receptor Type 11Receptor, Notch1ConceptsDe novo variantsNDD genesCardiac patterningDe novo damaging variantsDamaging de novo variantsCHD genesDamaging variantsGenesProtein truncatingGenetic originNovo variantsGene mutationsPatterningRecent studiesDendritic developmentVariantsMutationsNeurogenesisSynaptogenesisBonferroni correctionSystems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects
Edwards JJ, Rouillard AD, Fernandez NF, Wang Z, Lachmann A, Shankaran SS, Bisgrove BW, Demarest B, Turan N, Srivastava D, Bernstein D, Deanfield J, Giardini A, Porter G, Kim R, Roberts AE, Newburger JW, Goldmuntz E, Brueckner M, Lifton RP, Seidman CE, Chung WK, Tristani-Firouzi M, Yost HJ, Ma’ayan A, Gelb BD. Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects. JACC Basic To Translational Science 2020, 5: 376-386. PMID: 32368696, PMCID: PMC7188873, DOI: 10.1016/j.jacbts.2020.01.012.Peer-Reviewed Original ResearchSmall GTPaseSpecific molecular functionsWAVE2 complexMolecular functionsCHD genesSignal transductionComplex proteinsHeart disease pathogenesisCardiac developmentCausative variantsGenetic variantsGTPaseNovo variantsGenesDisease pathogenesisPrimary driverVariantsWAVE2TransductionComplexesKnockdownRegulatorProteinRegulationPathogenesis