Featured Publications
A retrospective cohort analysis of the Yale pediatric genomics discovery program
Al‐Ali S, Jeffries L, Faustino EVS, Ji W, Mis E, Konstantino M, Zerillo C, Jiang Y, Spencer‐Manzon M, Bale A, Zhang H, McGlynn J, McGrath JM, Tremblay T, Brodsky NN, Lucas CL, Pierce R, Deniz E, Khokha MK, Lakhani SA. A retrospective cohort analysis of the Yale pediatric genomics discovery program. American Journal Of Medical Genetics Part A 2022, 188: 2869-2878. PMID: 35899841, PMCID: PMC9474639, DOI: 10.1002/ajmg.a.62918.Peer-Reviewed Original ResearchMeSH KeywordsCohort StudiesGenetic TestingGenomicsHigh-Throughput Nucleotide SequencingHumansPhenotypeRetrospective StudiesConceptsRetrospective cohort analysisNext-generation sequencingCohort analysisSystem abnormalitiesImmune system abnormalitiesCardiovascular system abnormalitiesFunctional molecular analysesNovel genesPrecise molecular diagnosisClinical characteristicsFurther genetic evaluationDiscovery programsComplex patientsMultisystem diseaseDisease genesPediatric providersRare genetic diseaseNew diagnosisPhenotype relationshipsPatientsGenetic diseasesMolecular analysisDiagnosisParticipant demographicsNGS resultsRethinking what constitutes a diagnosis in the genomics era: a critical illness perspective.
Lakhani SA, Pierce R. Rethinking what constitutes a diagnosis in the genomics era: a critical illness perspective. Current Opinion In Pediatrics 2019, 31: 317-321. PMID: 31090571, DOI: 10.1097/mop.0000000000000754.Peer-Reviewed Original ResearchMeSH KeywordsChildCritical IllnessDiagnosisExome SequencingGenetic TestingGenomicsHumansRare DiseasesConceptsPediatric intensivistsIll childrenCritical care pediatriciansFirst clinical diagnosisTypes of patientsWhole-exome sequencingSevere congenital diseaseUnderlying genetic causePatient's conditionIllness perspectiveUndiagnosed diseasePatientsDescriptive diagnosisClinical diagnosisCongenital diseaseGenetic testingGenetic abnormalitiesDiagnosisExome sequencingGenetic causeNext-generation sequencingClinical geneticistsIntensivistsGenetic diagnosisDisease
2024
Unraveling the genetic tapestry of pediatric sarcomeric cardiomyopathies and masquerading phenocopies in Jordan
Azab B, Aburizeg D, Shaaban S, Ji W, Mustafa L, Isbeih N, Al-Akily A, Mohammad H, Jeffries L, Khokha M, Lakhani S, Al-Ammouri I. Unraveling the genetic tapestry of pediatric sarcomeric cardiomyopathies and masquerading phenocopies in Jordan. Scientific Reports 2024, 14: 15141. PMID: 38956129, PMCID: PMC11219879, DOI: 10.1038/s41598-024-64921-9.Peer-Reviewed Original ResearchConceptsExome sequencingSarcomere-related genesMitochondrial-related diseasesAt-risk family membersGenetic architectureGenetic landscapePathogenic variantsGene panelPediatric cardiomyopathyMolecular underpinningsGenetic testingPhenocopiesSarcomeric cardiomyopathiesGenesSequenceStorage disorderFamily membersAt-riskVariantsEarly interventionExomeFamilyGlycogen storage disorderHypertrophic cardiomyopathyCardiomyopathy
2021
Functional testing for variant prioritization in a family with long QT syndrome
Najari Beidokhti M, Bertalovitz AC, Ji W, McCormack J, Jeffries L, Sempou E, Khokha MK, McDonald TV, Lakhani SA. Functional testing for variant prioritization in a family with long QT syndrome. Molecular Genetics And Genomics 2021, 296: 823-836. PMID: 33876311, DOI: 10.1007/s00438-021-01780-3.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAMP-Activated Protein KinasesDNA Mutational AnalysisElectrocardiographyERG1 Potassium ChannelExome SequencingFamilyFemaleGenetic TestingHeart Function TestsHEK293 CellsHumansKCNQ1 Potassium ChannelLong QT SyndromeMiddle AgedMutationPedigreePhenotypePolymerase Chain ReactionPolymorphism, Single NucleotideProtein Serine-Threonine KinasesConceptsWhole-exome sequencingFunctional characterizationSilico analysisPrecise genetic etiologyHeterologous expression systemNext-generation sequencing platformsNovel genetic variantsDeleterious phenotypesFunction phenotypesExpression systemSequencing platformsSecond individualHeritable diseaseVariant prioritizationGenetic variantsLong QT syndromeExome sequencingGenetic etiologyGenetic settingClinical genetics settingPhenotypeFamilyGene panelFamily membersVariants
2018
A Novel Pathogenic UGT1A1 Variant in a Sudanese Child with Type I Crigler-Najjar Syndrome
Elfar W, Järvinen E, Ji W, Mosorin J, Sega AG, Iuga AC, Lobritto SJ, Konstantino M, Chan A, Finel M, Lakhani SA. A Novel Pathogenic UGT1A1 Variant in a Sudanese Child with Type I Crigler-Najjar Syndrome. Drug Metabolism And Disposition 2018, 47: dmd.118.084368. PMID: 30385458, DOI: 10.1124/dmd.118.084368.Peer-Reviewed Original ResearchConceptsUridine diphosphate glucuronosyltransferasesCrigler-Najjar syndromeSudanese childrenType I Crigler-Najjar syndromeSevere unconjugated hyperbilirubinemiaNovel homozygous variantClinical genetic testingAutosomal recessive disorderLiver transplantationClinical featuresPatient ethnicityHepatic enzymesUnconjugated hyperbilirubinemiaGlucuronidation activityGenetic testingBody's abilityHomozygous variantBilirubin conjugationRecessive disorderPatient variantsUGT1A1 variantsDisease phenotypeSanger sequencingUGT functionSyndrome