2024
CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow
Kim A, Sakin I, Viviano S, Tuncel G, Aguilera S, Goles G, Jeffries L, Ji W, Lakhani S, Kose C, Silan F, Oner S, Kaplan O, Group M, Ergoren M, Mishra-Gorur K, Gunel M, Sag S, Temel S, Deniz E. CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow. Life Science Alliance 2024, 7: e202402708. PMID: 39168639, PMCID: PMC11339347, DOI: 10.26508/lsa.202402708.Peer-Reviewed Original ResearchConceptsDevelopmental disabilitiesIntellectual disabilityPatient-derived fibroblastsMidbrain regionsBrain developmentDefective ciliogenesisCSF circulationDisabilityCSF flowAbnormal CSF flowNervous system developmentMutant tadpolesCiliated tissuesMultiple model systemsVariant functionPronephric ductUnrelated familiesCC2D1AExpression patternsCiliogenesisRenal dysplasiaLeft-right organizerFunctional analysisDisease mechanismsBrainUnraveling 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
2021
Functional testing for variant prioritization in a family with long QT syndrome
Najari Beidokhti M, Bertalovitz AC, Ji W, McCormack J, Jeffries L, Sempou E, Khokha MK, McDonald TV, Lakhani SA. Functional testing for variant prioritization in a family with long QT syndrome. Molecular Genetics And Genomics 2021, 296: 823-836. PMID: 33876311, DOI: 10.1007/s00438-021-01780-3.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAMP-Activated Protein KinasesDNA Mutational AnalysisElectrocardiographyERG1 Potassium ChannelExome SequencingFamilyFemaleGenetic TestingHeart Function TestsHEK293 CellsHumansKCNQ1 Potassium ChannelLong QT SyndromeMiddle AgedMutationPedigreePhenotypePolymerase Chain ReactionPolymorphism, Single NucleotideProtein Serine-Threonine KinasesConceptsWhole-exome sequencingFunctional characterizationSilico analysisPrecise genetic etiologyHeterologous expression systemNext-generation sequencing platformsNovel genetic variantsDeleterious phenotypesFunction phenotypesExpression systemSequencing platformsSecond individualHeritable diseaseVariant prioritizationGenetic variantsLong QT syndromeExome sequencingGenetic etiologyGenetic settingClinical genetics settingPhenotypeFamilyGene panelFamily membersVariants
2020
The latest FADS: Functional analysis of GLDN patient variants and classification of GLDN‐associated AMC as a type of viable fetal akinesia deformation sequence
Mis EK, Al‐Ali S, Ji W, Spencer‐Manzon M, Konstantino M, Khokha MK, Jeffries L, Lakhani SA. The latest FADS: Functional analysis of GLDN patient variants and classification of GLDN‐associated AMC as a type of viable fetal akinesia deformation sequence. American Journal Of Medical Genetics Part A 2020, 182: 2291-2296. PMID: 32812332, DOI: 10.1002/ajmg.a.61783.Peer-Reviewed Original ResearchConceptsFetal akinesia deformation sequenceArthrogryposis multiplex congenitaCohort of patientsScope of illnessPulmonary hypoplasiaAdditional patientsClinical featuresNeonatal supportNervous system developmentMultiplex congenitaCongenital contracturesPatientsHeterogenous conditionRecessive variantsPatient variantsFunctional evidenceCohortNovel variantsContractureFunctional dataSyndromeHypoplasiaIllnessVariantsFindingsDLG5 variants are associated with multiple congenital anomalies including ciliopathy phenotypes
Marquez J, Mann N, Arana K, Deniz E, Ji W, Konstantino M, Mis EK, Deshpande C, Jeffries L, McGlynn J, Hugo H, Widmeier E, Konrad M, Tasic V, Morotti R, Baptista J, Ellard S, Lakhani SA, Hildebrandt F, Khokha MK. DLG5 variants are associated with multiple congenital anomalies including ciliopathy phenotypes. Journal Of Medical Genetics 2020, 58: 453-464. PMID: 32631816, PMCID: PMC7785698, DOI: 10.1136/jmedgenet-2019-106805.Peer-Reviewed Original ResearchConceptsLoss of ciliaPatient tissuesPatient variantsCongenital heart diseaseMultiple organ systemsMultiple congenital anomaliesDLG5 variantsVariety of pathologiesNephrotic syndromeHeart diseaseCongenital anomaliesRespiratory tractKidney tissueOrgan systemsCystic kidneysPatient phenotypesKidneyDiseaseLimb abnormalitiesUnrelated familiesRescue experimentsCraniofacial malformationsCilia dysfunctionTissue-specific manifestationsTissue
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 casesPatientsEtiologySiblings 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