2021
D‐bifunctional protein deficiency caused by splicing variants in a neonate with severe peroxisomal dysfunction and persistent hypoglycemia
Werner KM, Cox AJ, Qian E, Jain P, Ji W, Tikhonova I, Castaldi C, Bilguvar K, Knight J, Ferdinandusse S, Fawaz R, Jiang Y, Gallagher PG, Bizzarro M, Gruen JR, Bale A, Zhang H. D‐bifunctional protein deficiency caused by splicing variants in a neonate with severe peroxisomal dysfunction and persistent hypoglycemia. American Journal Of Medical Genetics Part A 2021, 188: 357-363. PMID: 34623748, PMCID: PMC8678290, DOI: 10.1002/ajmg.a.62520.Peer-Reviewed Original ResearchMeSH KeywordsExonsHearing Loss, SensorineuralHumansHypoglycemiaInfant, NewbornPeroxisomal Multifunctional Protein-2Protein DeficiencyConceptsBifunctional protein deficiencyEarly mortalityClinical spectrumPersistent hypoglycemiaDBP deficiencyFat-soluble vitamin deficiencyImportant prognostic informationProtein deficiencyEnzyme deficiencyYears of lifePeroxisomal enzyme deficienciesResidual enzyme functionAbsent enzyme activityRapid whole-genome sequencingUnexplained hypoglycemiaEarly managementPrognostic informationVitamin deficiencyClinical severityNeonatal hypotoniaHigh burdenPeroxisomal dysfunctionPatient's fatherPsychomotor delayLong-chain fatty acids
2017
The 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 volumeMyoclonus
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 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