2024
Unraveling the genetic tapestry of pediatric sarcomeric cardiomyopathies and masquerading phenocopies in Jordan
Azab B, Aburizeg D, Shaaban S, Ji W, Mustafa L, Isbeih N, Al-Akily A, Mohammad H, Jeffries L, Khokha M, Lakhani S, Al-Ammouri I. Unraveling the genetic tapestry of pediatric sarcomeric cardiomyopathies and masquerading phenocopies in Jordan. Scientific Reports 2024, 14: 15141. PMID: 38956129, PMCID: PMC11219879, DOI: 10.1038/s41598-024-64921-9.Peer-Reviewed Original ResearchConceptsExome sequencingSarcomere-related genesMitochondrial-related diseasesAt-risk family membersGenetic architectureGenetic landscapePathogenic variantsGene panelPediatric cardiomyopathyMolecular underpinningsGenetic testingPhenocopiesSarcomeric cardiomyopathiesGenesSequenceStorage disorderFamily membersAt-riskVariantsEarly interventionExomeFamilyGlycogen storage disorderHypertrophic cardiomyopathyCardiomyopathy
2023
CFAP45, a heterotaxy and congenital heart disease gene, affects cilia stability
Deniz E, Pasha M, Guerra M, Viviano S, Ji W, Konstantino M, Jeffries L, Lakhani S, Medne L, Skraban C, Krantz I, Khokha M. CFAP45, a heterotaxy and congenital heart disease gene, affects cilia stability. Developmental Biology 2023, 499: 75-88. PMID: 37172641, PMCID: PMC10373286, DOI: 10.1016/j.ydbio.2023.04.006.Peer-Reviewed Original ResearchConceptsLeft-right organizerCilia stabilityLeft-right patterningCongenital heart disease genesApical surfaceCell apical surfaceLive confocal imagingLeftward fluid flowHeart disease genesRecessive missense mutationLethal birth defectMotile monociliaProtein familyEarly embryogenesisMulticiliated cellsCiliary axonemeDisease genesFrog embryosGenetic underpinningsWhole-exome sequencingMissense mutationsConfocal imagingEmbryosCiliaCongenital heart disease
2022
A retrospective cohort analysis of the Yale pediatric genomics discovery program
Al‐Ali S, Jeffries L, Faustino EVS, Ji W, Mis E, Konstantino M, Zerillo C, Jiang Y, Spencer‐Manzon M, Bale A, Zhang H, McGlynn J, McGrath JM, Tremblay T, Brodsky NN, Lucas CL, Pierce R, Deniz E, Khokha MK, Lakhani SA. A retrospective cohort analysis of the Yale pediatric genomics discovery program. American Journal Of Medical Genetics Part A 2022, 188: 2869-2878. PMID: 35899841, PMCID: PMC9474639, DOI: 10.1002/ajmg.a.62918.Peer-Reviewed Original ResearchConceptsRetrospective cohort analysisNext-generation sequencingCohort analysisSystem abnormalitiesImmune system abnormalitiesCardiovascular system abnormalitiesFunctional molecular analysesNovel genesPrecise molecular diagnosisClinical characteristicsFurther genetic evaluationDiscovery programsComplex patientsMultisystem diseaseDisease genesPediatric providersRare genetic diseaseNew diagnosisPhenotype relationshipsPatientsGenetic diseasesMolecular analysisDiagnosisParticipant demographicsNGS resultsTBX5 variant with the novel phenotype of mixed-type total anomalous pulmonary venous return in Holt-Oram Syndrome and variable intrafamilial heart defects
Azab B, Aburizeg D, Ji W, Jeffries L, Isbeih NJ, Al-Akily AS, Mohammad H, Abu Osba Y, Shahin MA, Dardas Z, Hatmal MM, Al-Ammouri I, Lakhani S. TBX5 variant with the novel phenotype of mixed-type total anomalous pulmonary venous return in Holt-Oram Syndrome and variable intrafamilial heart defects. Molecular Medicine Reports 2022, 25: 210. PMID: 35514310, PMCID: PMC9133962, DOI: 10.3892/mmr.2022.12726.Peer-Reviewed Original ResearchConceptsHolt-Oram syndromeMolecular etiologyT-box domainWild-type proteinT-box transcription factorGenetic investigationsTrio-based whole-exome sequencingNonsense variantTranscription factorsIntrafamilial levelTBX5 proteinNovel phenotypesProtein's abilityFirst genetic investigationMutant dimersNon-syndromic presentationsProtein modelingWhole-exome sequencingComplete phenotypingSubsequent genetic investigationsTbx5Novel associationsPowerful approachWide phenotypic spectrumNon-covalent bonds
2020
Ring chromosome formation by intra‐strand repairing of subtelomeric double stand breaks and clinico‐cytogenomic correlations for ring chromosome 9
Chai H, Ji W, Wen J, DiAdamo A, Grommisch B, Hu Q, Szekely AM, Li P. Ring chromosome formation by intra‐strand repairing of subtelomeric double stand breaks and clinico‐cytogenomic correlations for ring chromosome 9. American Journal Of Medical Genetics Part A 2020, 182: 3023-3028. PMID: 32978894, DOI: 10.1002/ajmg.a.61890.Peer-Reviewed Original ResearchDYNC1H1‐related disorders: A description of four new unrelated patients and a comprehensive review of previously reported variants
Amabile S, Jeffries L, McGrath JM, Ji W, Spencer‐Manzon M, Zhang H, Lakhani SA. DYNC1H1‐related disorders: A description of four new unrelated patients and a comprehensive review of previously reported variants. American Journal Of Medical Genetics Part A 2020, 182: 2049-2057. PMID: 32656949, DOI: 10.1002/ajmg.a.61729.Peer-Reviewed Original ResearchConceptsSpinal muscular atrophyIntellectual disabilityUnrelated patientsSingle-center experienceNew unrelated patientsCenter experienceDYNC1H1 geneCNS disordersCombined disordersCortical developmentDisease-causing variantsVariable syndromeNeuromuscular diseaseNeuromuscular phenotypePatientsMuscular atrophyHeterozygous variantsDYNC1H1Medical literatureCharcot-MarieDisordersType 20Novel variantsPhenotypeReportA novel variant in MAP3K7 associated with an expanded cardiospondylocarpofacial syndrome phenotype
AbuBakr F, Jeffries L, Ji W, McGrath JM, Lakhani SA. A novel variant in MAP3K7 associated with an expanded cardiospondylocarpofacial syndrome phenotype. Molecular Case Studies 2020, 6: mcs.a005207. PMID: 32299812, PMCID: PMC7304360, DOI: 10.1101/mcs.a005207.Peer-Reviewed Original ResearchConceptsCardiospondylocarpofacial syndromePathogenic variantsValvular heart diseaseDistinctive cutaneous findingsLikely pathogenic variantsCutaneous findingsFlexion contractureHeart diseaseSecond toePatientsShort statureGrowth factorProtein kinase kinase kinase 7Facial dysmorphismSyndrome phenotypeMissense variantsSyndromeKinase 7Kinase 1Novel variantsSixth variantSplice variantsPhenotypeFrame deletionInflammation
2019
Identification of a novel MYOC variant in a Hispanic family with early-onset primary open-angle glaucoma with elevated intraocular pressure
Criscione J, Ji W, Jeffries L, McGrath JM, Soloway S, Pusztai L, Lakhani S. Identification of a novel MYOC variant in a Hispanic family with early-onset primary open-angle glaucoma with elevated intraocular pressure. Molecular Case Studies 2019, 5: a004374. PMID: 31653660, PMCID: PMC6913140, DOI: 10.1101/mcs.a004374.Peer-Reviewed Original ResearchConceptsPrimary open-angle glaucomaEarly-onset primary open-angle glaucomaOpen-angle glaucomaGenetic testingElevated intraocular pressureJuvenile-onset primary open-angle glaucomaFurther genetic testingAutosomal dominant patternFemale patientsIntraocular pressureIrreversible blindnessFamily historyEye disordersMYOC variantsMyocilin geneGlaucomaPOAG phenotypeHispanic familiesOlfactomedin domainPrevious findingsDominant patternVariant segregatesMost casesPatientsEtiologyIdentification of novel mutations and phenotype in the steroid resistant nephrotic syndrome gene NUP93: a case report
Sandokji I, Marquez J, Ji W, Zerillo CA, Konstantino M, Lakhani SA, Khokha MK, Warejko JK. Identification of novel mutations and phenotype in the steroid resistant nephrotic syndrome gene NUP93: a case report. BMC Nephrology 2019, 20: 271. PMID: 31315584, PMCID: PMC6637548, DOI: 10.1186/s12882-019-1458-z.Peer-Reviewed Case Reports and Technical NotesSiblings with lethal primary pulmonary hypoplasia and compound heterozygous variants in the AARS2 gene: further delineation of the phenotypic spectrum
Kiraly-Borri C, Jevon G, Ji W, Jeffries L, Ricciardi JL, Konstantino M, Ackerman KG, Lakhani SA. Siblings with lethal primary pulmonary hypoplasia and compound heterozygous variants in the AARS2 gene: further delineation of the phenotypic spectrum. Molecular Case Studies 2019, 5: a003699. PMID: 30819764, PMCID: PMC6549552, DOI: 10.1101/mcs.a003699.Peer-Reviewed Original ResearchConceptsPrimary pulmonary hypoplasiaPulmonary hypoplasiaPhenotypic spectrumEvidence of cardiomyopathyPremature ovarian insufficiencyAbsence of cardiomyopathyCompound heterozygous variantsWhole-exome sequencingOvarian insufficiencyAARS2 geneCompound HeterozygousHeterozygous variantsCardiomyopathyNewborn siblingsCarrier statusFurther delineationHypoplasiaUnaffected siblingsMitochondrial cardiomyopathySiblingsFirst reportLeukoencephalopathy