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
2015
Whole-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 ResearchMeSH KeywordsComputational BiologyExomeFemaleGenetic Association StudiesGenetic Diseases, InbornGenomicsGenotypeHigh-Throughput Nucleotide SequencingHumansMaleMutationPhenotypeConceptsDisease 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
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