2022
Disrupted Topological Organization of White Matter Network in Angelman Syndrome
Wei L, Du X, Yang Z, Ding M, Yang B, Wang J, Long S, Qiao Z, Jiang Y, Wang Y, Wang H. Disrupted Topological Organization of White Matter Network in Angelman Syndrome. Journal Of Magnetic Resonance Imaging 2022, 57: 1212-1221. PMID: 35856797, DOI: 10.1002/jmri.28360.Peer-Reviewed Original ResearchMeSH KeywordsAngelman SyndromeBrainChildChild, PreschoolDiffusion Tensor ImagingFemaleHumansMaleProspective StudiesWhite Matter
2019
De Novo Missense Variants in FBXW11 Cause Diverse Developmental Phenotypes Including Brain, Eye, and Digit Anomalies
Holt RJ, Young RM, Crespo B, Ceroni F, Curry CJ, Bellacchio E, Bax DA, Ciolfi A, Simon M, Fagerberg CR, van Binsbergen E, De Luca A, Memo L, Dobyns WB, Mohammed AA, Clokie SJH, Seco C, Jiang YH, Sørensen KP, Andersen H, Sullivan J, Powis Z, Chassevent A, Smith-Hicks C, Petrovski S, Antoniadi T, Shashi V, Gelb BD, Wilson SW, Gerrelli D, Tartaglia M, Chassaing N, Calvas P, Ragge NK. De Novo Missense Variants in FBXW11 Cause Diverse Developmental Phenotypes Including Brain, Eye, and Digit Anomalies. American Journal Of Human Genetics 2019, 105: 640-657. PMID: 31402090, PMCID: PMC6731360, DOI: 10.1016/j.ajhg.2019.07.005.Peer-Reviewed Original ResearchConceptsF-box (SCF) ubiquitin ligase complexF-box proteinsMultiple developmental processesPectoral fin developmentSubstrate-binding domainUbiquitin ligase complexGli transcription factorsHuman developmental disordersSecond-generation sequencingDe novo missense variantsWhole-genome sequencingSkp1-CullinDevelopmental phenotypesLigase complexFin developmentResidue clustersTranscription factorsProteasomal degradationEye developmentNovo missense variantsDevelopmental processesFBXW11Genome sequencingEmbryonic tissuesUnderdeveloped eyes
2018
Role of PUF60 gene in Verheij syndrome: a case report of the first Chinese Han patient with a de novo pathogenic variant and review of the literature
Xu Q, Li CY, Wang Y, Li HP, Wu BB, Jiang YH, Xu X. Role of PUF60 gene in Verheij syndrome: a case report of the first Chinese Han patient with a de novo pathogenic variant and review of the literature. BMC Medical Genomics 2018, 11: 92. PMID: 30352594, PMCID: PMC6199733, DOI: 10.1186/s12920-018-0421-3.Peer-Reviewed Original ResearchConceptsChinese Han patientsHan patientsNovo pathogenic variantsClinical whole exome sequencingDysmorphic facial featuresNovo nonsense variantWhole-exome sequencingRare microdeletion syndromeClinical featuresCase reportSpinal anomaliesPathogenic variantsRelated disordersGrowth retardationPUF60 geneConclusionsOur findingsSyndromeExome sequencingNonsense variantMicrodeletion syndromeIntellectual disabilityPatientsFunction mutationsPUF60Chromosome 8q24.3Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing
Wu J, Yu P, Jin X, Xu X, Li J, Li Z, Wang M, Wang T, Wu X, Jiang Y, Cai W, Mei J, Min Q, Xu Q, Zhou B, Guo H, Wang P, Zhou W, Hu Z, Li Y, Cai T, Wang Y, Xia K, Jiang YH, Sun ZS. Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing. Journal Of Genetics And Genomics 2018, 45: 527-538. PMID: 30392784, DOI: 10.1016/j.jgg.2018.09.002.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdolescentAdultAsian PeopleAutism Spectrum DisorderCell Cycle ProteinsChildChild, PreschoolChinaDNA Copy Number VariationsDNA-Binding ProteinsFemaleGenetic Predisposition to DiseaseHumansMaleMutationNerve Tissue ProteinsTranscription FactorsWhole Genome SequencingYoung AdultConceptsChromosomal rearrangement eventsDe novo chromosomal translocationsGenomic structural variantsNovo chromosomal translocationWhole genome sequencing datasetsFull genetic spectrumRare deleterious variantsChromosomal structure analysisHigh mutation rateSporadic autism spectrum disordersWhole-genome sequencingChromatin remodelingCentrosomal functionWhole genomeRare inherited mutationsDe novo mutationsRearrangement eventsSequencing datasetsDeleterious variantsGenomic variantsMutation rateStructural variantsGenomic landscapeNovo CNVsRisk genes
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 testingNovel clinical manifestations in patients with KCNA2 mutations
Sachdev M, Gaínza-Lein M, Tchapyjnikov D, Jiang YH, Loddenkemper T, Mikati MA. Novel clinical manifestations in patients with KCNA2 mutations. Seizure 2017, 51: 74-76. PMID: 28806589, DOI: 10.1016/j.seizure.2017.07.018.Peer-Reviewed Original ResearchMeSH KeywordsChildChild, PreschoolEpilepsyFemaleHumansKv1.2 Potassium ChannelMaleMutationYoung AdultConceptsGeneralized tonic-clonic seizuresTonic-clonic seizuresElectrical status epilepticusNovel clinical manifestationYear old maleStatus epilepticusKCNA2 mutationsClonic seizuresClinical manifestationsMyoclonic-astatic seizuresStatus epilepticus episodesYear old femaleYears of ageAstatic seizuresSeizure typesEpileptic manifestationsFocal seizuresPatient 1Patient 2Patient 3Clinical criteriaSevere manifestationsEpileptic encephalopathyBlood samplesPatientsNeonatal nonepileptic myoclonus is a prominent clinical feature of KCNQ2 gain‐of‐function variants R201C and R201H
Mulkey SB, Ben‐Zeev B, Nicolai J, Carroll JL, Grønborg S, Jiang Y, Joshi N, Kelly M, Koolen DA, Mikati MA, Park K, Pearl PL, Scheffer IE, Spillmann RC, Taglialatela M, Vieker S, Weckhuysen S, Cooper EC, Cilio MR. Neonatal nonepileptic myoclonus is a prominent clinical feature of KCNQ2 gain‐of‐function variants R201C and R201H. Epilepsia 2017, 58: 436-445. PMID: 28139826, PMCID: PMC5339037, DOI: 10.1111/epi.13676.Peer-Reviewed Original ResearchConceptsNonepileptic myoclonusClinical presentationFunction variantsMultifocal epileptiform dischargesProminent clinical featureDistinct clinical presentationsProfound developmental delayBurst-suppression patternInstitutional review boardNeonatal encephalopathyClinical featuresEpileptic spasmsNeonatal periodNeonatal seizuresRespiratory dysfunctionPatient RegistryMedical recordsNeonatal presentationElectrophysiologic propertiesEpileptiform dischargesParoxysmal movementsTherapeutic approachesPatientsBrain volumeMyoclonus
2016
Chromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge
Xu Q, Goldstein J, Wang P, Gadi IK, Labreche H, Rehder C, Wang WP, McConkie A, Xu X, Jiang YH. Chromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge. Pediatric Research 2016, 80: 371-381. PMID: 27119313, PMCID: PMC5382808, DOI: 10.1038/pr.2016.101.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlgorithmsAutistic DisorderChildChild, PreschoolChromatinComparative Genomic HybridizationCounselingDevelopmental DisabilitiesDNA Copy Number VariationsFemaleGene DeletionGene RearrangementHistone-Lysine N-MethyltransferaseHumansInfantIntellectual DisabilityMaleMicroarray AnalysisNeurodevelopmental DisordersPedigreeProtein MethyltransferasesConceptsNeurodevelopmental disordersAutism spectrum disorderIntellectual disabilityDevelopmental disabilitiesCopy number variationsChromosomal microarray analysisEtiological evaluationClinical evaluationClinical significanceUnknown significanceCNV analysisGenetics clinicEtiology of ASDCounseling familiesDisordersVariable penetranceClinicMicroarray analysisNovel deletionSpectrum disorderDisabilityCounseling challengesFurther supportEtiologyCohort
2015
Quinidine in the treatment of KCNT1‐positive epilepsies
Mikati MA, Jiang YH, Carboni M, Shashi V, Petrovski S, Spillmann R, Milligan CJ, Li M, Grefe A, McConkie A, Berkovic S, Scheffer I, Mullen S, Bonner M, Petrou S, Goldstein D. Quinidine in the treatment of KCNT1‐positive epilepsies. Annals Of Neurology 2015, 78: 995-999. PMID: 26369628, PMCID: PMC4811613, DOI: 10.1002/ana.24520.Peer-Reviewed Original ResearchConceptsEpilepsy of infancySecondary generalized seizuresDrug-resistant epilepsySeizure frequencyGeneralized seizuresFocal seizuresKCNT1 mutationsSeizure evaluationSeizure diariesTargeted drugsTherapeutic benefitDevelopmental regressionEpilepsyGain of functionQuinidineEarly childhoodSeizuresPatientsMutationsPractical 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 testing
2014
A CACNA1C Variant Associated with Reduced Voltage-Dependent Inactivation, Increased CaV1.2 Channel Window Current, and Arrhythmogenesis
Hennessey JA, Boczek NJ, Jiang YH, Miller JD, Patrick W, Pfeiffer R, Sutphin BS, Tester DJ, Barajas-Martinez H, Ackerman MJ, Antzelevitch C, Kanter R, Pitt GS. A CACNA1C Variant Associated with Reduced Voltage-Dependent Inactivation, Increased CaV1.2 Channel Window Current, and Arrhythmogenesis. PLOS ONE 2014, 9: e106982. PMID: 25184293, PMCID: PMC4153713, DOI: 10.1371/journal.pone.0106982.Peer-Reviewed Original ResearchMeSH KeywordsAutistic DisorderCalcium Channels, L-TypeChild, PreschoolFemaleHumansInfantLong QT SyndromeMaleMembrane PotentialsMutationSyndactylyConceptsSudden unexplained infant deathVoltage-dependent inactivationLong QT syndromeWindow currentTimothy syndromeCav1.2 L-type Ca2Multiple dental cariesLower extremity weaknessGain of functionCertain clinical settingsEpisodes of rhabdomyolysisUnexplained infant deathL-type Ca2Channel window currentAge 5 yearsYears of ageAppreciation of mechanismsMonths of ageCandidate gene sequencingCardiac ion channelsRecurrent VTExtremity weaknessSpastic diplegiaExtracardiac featuresDental cariesA genomic copy number variant analysis implicates the MBD5 and HNRNPUgenes in Chinese children with infantile spasms and expands the clinical spectrum of 2q23.1 deletion
Du X, An Y, Yu L, Liu R, Qin Y, Guo X, Sun D, Zhou S, Wu B, Jiang YH, Wang Y. A genomic copy number variant analysis implicates the MBD5 and HNRNPUgenes in Chinese children with infantile spasms and expands the clinical spectrum of 2q23.1 deletion. BMC Medical Genomics 2014, 15: 62. PMID: 24885232, PMCID: PMC4061518, DOI: 10.1186/1471-2350-15-62.Peer-Reviewed Original ResearchMeSH Keywords1-Alkyl-2-acetylglycerophosphocholine EsteraseAge of OnsetBrainChild, PreschoolChromosome DeletionChromosomes, Human, Pair 1Chromosomes, Human, Pair 17Chromosomes, Human, Pair 2DNA Copy Number VariationsDNA-Binding ProteinsFaciesFemaleFoot Deformities, CongenitalHand Deformities, CongenitalHeterogeneous-Nuclear RibonucleoproteinsHumansInfantInfant, NewbornMagnetic Resonance ImagingMaleMicrotubule-Associated ProteinsPhenotypeSpasms, InfantileConceptsInfantile spasmsEpileptic encephalopathyChinese childrenCNV lossDistinct clinical presentationsCopy number variantsPathogenicity of CNVsAutism spectrum disorderCausative genesMajority of casesWhole-exome sequencingRole of CNVsGeneralized seizuresClinical featuresClinical presentationClinical spectrumPrimary diagnosisSevere developmental disabilitiesSpasmConclusionOur findingsMBD5 geneReal-time qPCRExome sequencingGenetic factorsDifferent ethnic backgrounds
2008
De novo and complex imbalanced chromosomal rearrangements revealed by array CGH in a patient with an abnormal phenotype and apparently “balanced” paracentric inversion of 14(q21q23)
Jiang Y, Martinez JE, Ou Z, Cooper ML, Kang S, Pursley A, Cheung SW. De novo and complex imbalanced chromosomal rearrangements revealed by array CGH in a patient with an abnormal phenotype and apparently “balanced” paracentric inversion of 14(q21q23). American Journal Of Medical Genetics Part A 2008, 146A: 1986-1993. PMID: 18627051, DOI: 10.1002/ajmg.a.32408.Peer-Reviewed Original ResearchAbnormalities, MultipleChild, PreschoolChromosome BreakageChromosome DeletionChromosome InversionChromosomes, Artificial, BacterialChromosomes, Human, Pair 14Developmental DisabilitiesFemaleGenome, HumanHumansIn Situ Hybridization, FluorescenceKaryotypingMuscle HypotoniaOligonucleotide Array Sequence AnalysisPhenotype