2017
Does age affect response to quinidine in patients with KCNT1 mutations? Report of three new cases and review of the literature
Abdelnour E, Gallentine W, McDonald M, Sachdev M, Jiang YH, Mikati MA. Does age affect response to quinidine in patients with KCNT1 mutations? Report of three new cases and review of the literature. Seizure 2017, 55: 1-3. PMID: 29291456, DOI: 10.1016/j.seizure.2017.11.017.Peer-Reviewed Original ResearchConceptsKCNT1 mutationsEpilepsy of infancyRetrospective chart reviewPotassium channel blockerYears of agePotential therapeutic agentFunction mutationsMigrating Focal SeizuresKCNT1 gainKCNT1 geneQuinidine initiationChart reviewRefractory seizuresSeizure frequencyQuinidine therapySeizure responseSeizure typesFocal seizuresEpilepsy syndromesVideo-EEGChannel blockersNew casesTherapeutic agentsPatientsAdditional childrenLooking 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 testingThe importance of managing the patient and not the gene: expanded phenotype of GLE1-associated arthrogryposis
Tan Q, McConkie-Rosell A, Juusola J, Gustafson KE, Pizoli CE, Buckley AF, Jiang YH. The importance of managing the patient and not the gene: expanded phenotype of GLE1-associated arthrogryposis. Molecular Case Studies 2017, 3: a002063. PMID: 28729373, PMCID: PMC5701308, DOI: 10.1101/mcs.a002063.Peer-Reviewed Original ResearchConceptsAnterior horn cell diseaseCell diseasePathogenic variantsMotor neuron diseaseBiallelic missense mutationsSpinal muscular atrophyWhole-exome sequencingMotor weaknessRespiratory supportRespiratory difficultyNeuron diseaseMotor phenotypePerinatal periodPrenatal symptomsContracture syndromeMuscle biopsySevere formFetal akinesiaMuscular atrophyDiseaseMRNA exportLethal arthrogryposisTranslation initiationPerinatal lethalityArthrogryposisNeonatal 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 volumeMyoclonusGenetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing
Wang Y, Du X, Bin R, Yu S, Xia Z, Zheng G, Zhong J, Zhang Y, Jiang YH, Wang Y. Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing. Scientific Reports 2017, 7: 40319. PMID: 28074849, PMCID: PMC5225856, DOI: 10.1038/srep40319.Peer-Reviewed Original ResearchConceptsNGS panelCaucasian childrenEtiology of epilepsyLikely pathogenic variantsTargeted exome sequencingGenetic variantsSingle nucleotide variantsUnknown etiologyEpilepsy patientsSpecific treatmentEpilepsyEpilepsy disordersPathogenic variantsPathologic variantsGenetic susceptibilityEpilepsy genesExome sequencingEtiologyGenetic factorsEpilepsy familiesChinese childrenCandidate genesClinicNovel candidate genesChildren
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
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 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 ResearchConceptsSudden 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
2013
Deficiency of Asparagine Synthetase Causes Congenital Microcephaly and a Progressive Form of Encephalopathy
Ruzzo EK, Capo-Chichi JM, Ben-Zeev B, Chitayat D, Mao H, Pappas AL, Hitomi Y, Lu YF, Yao X, Hamdan FF, Pelak K, Reznik-Wolf H, Bar-Joseph I, Oz-Levi D, Lev D, Lerman-Sagie T, Leshinsky-Silver E, Anikster Y, Ben-Asher E, Olender T, Colleaux L, Décarie JC, Blaser S, Banwell B, Joshi RB, He XP, Patry L, Silver RJ, Dobrzeniecka S, Islam MS, Hasnat A, Samuels ME, Aryal DK, Rodriguiz RM, Jiang YH, Wetsel WC, McNamara JO, Rouleau GA, Silver DL, Lancet D, Pras E, Mitchell GA, Michaud JL, Goldstein DB. Deficiency of Asparagine Synthetase Causes Congenital Microcephaly and a Progressive Form of Encephalopathy. Neuron 2013, 80: 429-441. PMID: 24139043, PMCID: PMC3820368, DOI: 10.1016/j.neuron.2013.08.013.Peer-Reviewed Original ResearchConceptsCongenital microcephalyProgressive cerebral atrophyStructural brain abnormalitiesCerebral atrophyNeuronal damageEnhanced excitabilityIntractable seizuresAsparagine depletionNeurological impairmentBrain abnormalitiesCortical thicknessLoss of functionASNS deficiencyProgressive formMutant micePatient phenotypesIntellectual disabilityASNS geneMicrocephalyMissense mutationsBrainDeficiencyAspartate/MutationsRecessive mutations