2020
Exome sequencing analysis on products of conception: a cohort study to evaluate clinical utility and genetic etiology for pregnancy loss
Zhao C, Chai H, Zhou Q, Wen J, Reddy UM, Kastury R, Jiang Y, Mak W, Bale AE, Zhang H, Li P. Exome sequencing analysis on products of conception: a cohort study to evaluate clinical utility and genetic etiology for pregnancy loss. Genetics In Medicine 2020, 23: 435-442. PMID: 33100332, DOI: 10.1038/s41436-020-01008-6.Peer-Reviewed Original ResearchConceptsProducts of conceptionAbnormality detection rateLikely pathogenic variantsSpontaneous abortionPregnancy lossPathogenic variantsExome sequencingClinical utilityGenetic etiologyExome sequencing analysisPathogenic copy number variantsCohort studyFetal deathRenal diseaseMethodsA cohortSubsequent pregnancyCardiac anomaliesMonogenic etiologyMetabolic disordersRecurrence riskMultisystem abnormalitiesDiagnostic valueConclusionThese resultsMonogenic causesStillbirthAlternative transcripts in variant interpretation: the potential for missed diagnoses and misdiagnoses
Schoch K, Tan Q, Stong N, Deak KL, McConkie-Rosell A, McDonald MT, Goldstein D, Jiang Y, Shashi V. Alternative transcripts in variant interpretation: the potential for missed diagnoses and misdiagnoses. Genetics In Medicine 2020, 22: 1269-1275. PMID: 32366967, PMCID: PMC7335342, DOI: 10.1038/s41436-020-0781-x.Peer-Reviewed Original Research
2018
A comprehensive iterative approach is highly effective in diagnosing individuals who are exome negative
Shashi V, Schoch K, Spillmann R, Cope H, Tan Q, Walley N, Pena L, McConkie-Rosell A, Jiang YH, Stong N, Need AC, Goldstein DB. A comprehensive iterative approach is highly effective in diagnosing individuals who are exome negative. Genetics In Medicine 2018, 21: 161-172. PMID: 29907797, PMCID: PMC6295275, DOI: 10.1038/s41436-018-0044-2.Peer-Reviewed Original ResearchSystematic reconstruction of autism biology from massive genetic mutation profiles
Luo W, Zhang C, Jiang YH, Brouwer CR. Systematic reconstruction of autism biology from massive genetic mutation profiles. Science Advances 2018, 4: e1701799. PMID: 29651456, PMCID: PMC5895441, DOI: 10.1126/sciadv.1701799.Peer-Reviewed Original ResearchConceptsComplex genetic diseasesWhole-exome studiesHundreds of variantsGene functionNovel genesSubpathway levelGene groupsSame geneCanonical pathwaysPathway levelAutism-related mutationsSecond messenger systemsGenesGenetic diseasesASD biologyCAMP second messenger systemBiologyGenetic associationMutationsMultiple independent analysesMost variantsPathwayVariant levelsSynaptic functionGenetic mutation profiles
2017
Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases
Pena LDM, Jiang YH, Schoch K, Spillmann RC, Walley N, Stong N, Rapisardo Horn S, Sullivan JA, McConkie-Rosell A, Kansagra S, Smith EC, El-Dairi M, Bellet J, Keels MA, Jasien J, Kranz PG, Noel R, Nagaraj SK, Lark RK, Wechsler DSG, del Gaudio D, Leung ML, Hendon LG, Parker CC, Jones KL, Goldstein D, Shashi V. Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases. Genetics In Medicine 2017, 20: 464-469. PMID: 28914269, PMCID: PMC5851806, DOI: 10.1038/gim.2017.128.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMagnetic resonance image changesPathogenic variantsSanger sequencingPhenotype-first approachFurther diagnostic testingNew clinical findingsInfantile neuroaxonal dystrophyHeterozygous pathogenic variantsInfantile systemic hyalinosisSingle-gene testingClinical suspicionClinical findingsConclusionThese casesCerebellar atrophyWhite matter leukoencephalopathyNeuroaxonal dystrophyProgressive ataxiaMolecular testingSystemic hyalinosisNGS testingNovel homozygous deletionUndiagnosed diseaseClinical diagnosisDiagnostic testing
2016
Not the End of the Odyssey: Parental Perceptions of Whole Exome Sequencing (WES) in Pediatric Undiagnosed Disorders
Rosell AM, Pena LD, Schoch K, Spillmann R, Sullivan J, Hooper SR, Jiang Y, Mathey‐Andrews N, Goldstein DB, Shashi V. Not the End of the Odyssey: Parental Perceptions of Whole Exome Sequencing (WES) in Pediatric Undiagnosed Disorders. Journal Of Genetic Counseling 2016, 25: 1019-1031. PMID: 26868367, DOI: 10.1007/s10897-016-9933-1.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingLikely diagnosisParental perceptionsRetrospective semi-structured interviewsMedical careWES findingsExome sequencingParents of childrenNegative genetic testing resultsGenetic testing resultsChild's medical careRare genetic disorderClinical diagnostic categoriesParental expectationsSense of isolationParental motivationDefinite diagnosisPrimary diagnosisRare disorderSemi-structured interviewsEducational professionalsSpecific treatmentUndiagnosed disordersPossible diagnosisRecurrence risk
2015
Practical considerations in the clinical application of whole‐exome sequencing
Shashi V, McConkie‐Rosell A, Schoch K, Kasturi V, Rehder C, Jiang YH, Goldstein DB, McDonald MT. Practical considerations in the clinical application of whole‐exome sequencing. Clinical Genetics 2015, 89: 173-181. PMID: 25678066, DOI: 10.1111/cge.12569.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingClinical informationMedical genetics practiceWES resultsUtility of WESMolecular diagnostic rateClinical whole exome sequencingMedical geneticistsAdditional laboratory testsRetrospective studyDefinite diagnosisClinical dataLikely diagnosisPossible diagnosisClinical categoriesDiagnostic rateFurther laboratory testingPatientsUncertain significanceGenetic practiceDiagnosisClinical applicationFamily membersLaboratory resultsLaboratory testingWhole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios
Zhu X, Petrovski S, Xie P, Ruzzo EK, Lu YF, McSweeney KM, Ben-Zeev B, Nissenkorn A, Anikster Y, Oz-Levi D, Dhindsa RS, Hitomi Y, Schoch K, Spillmann RC, Heimer G, Marek-Yagel D, Tzadok M, Han Y, Worley G, Goldstein J, Jiang YH, Lancet D, Pras E, Shashi V, McHale D, Need AC, Goldstein DB. Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios. Genetics In Medicine 2015, 17: 774-781. PMID: 25590979, PMCID: PMC4791490, DOI: 10.1038/gim.2014.191.Peer-Reviewed Original ResearchConceptsDisease genesWhole-exome sequencingDamaging de novo mutationsNovel bioinformatics approachNovel disease genesAppropriate bioinformatics analysisNew gene-disease associationsClinical sequence dataGene-disease associationsDisease-causing genesNovel genesIntolerant genesBioinformatics approachSequence dataBioinformatics analysisDe novo mutationsGenomic interpretationPattern of genotypesSimilar phenotypeGenesGenetic diseasesDiagnostic genotypesUndiagnosed genetic diseasesNovo mutationsCandidate genotypes
2013
The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders
Shashi V, McConkie-Rosell A, Rosell B, Schoch K, Vellore K, McDonald M, Jiang YH, Xie P, Need A, Goldstein DB. The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders. Genetics In Medicine 2013, 16: 176-182. PMID: 23928913, DOI: 10.1038/gim.2013.99.Peer-Reviewed Original ResearchConceptsUndiagnosed genetic disordersDiagnostic evaluationNext-generation sequencingGenetic diagnostic evaluationGenetic testingGenetic disordersGenetic diagnosisGeneral genetics clinicsTertiary medical centerFirst clinical visitComprehensive clinical evaluationUnselected consecutive patientsTraditional genetic testingConsecutive patientsInitial visitClinical visitsClinical evaluationFirst visitDiagnostic yieldMedical CenterNumber of visitsDiagnosis rateGenetics clinicDiagnostic algorithmPatients
2012
Mutations of ANK3 identified by exome sequencing are associated with autism susceptibility
Bi C, Wu J, Jiang T, Liu Q, Cai W, Yu P, Cai T, Zhao M, Jiang Y, Sun ZS. Mutations of ANK3 identified by exome sequencing are associated with autism susceptibility. Human Mutation 2012, 33: 1635-1638. PMID: 22865819, DOI: 10.1002/humu.22174.Peer-Reviewed Original ResearchConceptsExtensive bioinformatics analysisNext-generation sequencing technologiesExtreme genetic heterogeneityStrong genetic etiologyGene discoveryWhole-exome sequencesDifferent missense mutationsBioinformatics analysisSequencing technologiesAutism susceptibilityMissense mutationsANK3Genetic heterogeneityMutationsNovo mutationsExome sequencingMolecular pathophysiologyGenetic causeGenetic etiologyASD susceptibilitySynaptic functionNovel mutationsNeurodevelopmental disordersGenesSequencing