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 cardiomyopathyCardiomyopathyA Novel Variant in the Cyto-Tail of SMO Gene Underlying Isolated Postaxial Polydactyly
Khan M, Abdullah, Khan H, Zaman A, Ahmed S, Iqbal P, Bilal M, Ullah K, Hasni M, Ullah I, Mis E, Lakhani S, Ahmad W. A Novel Variant in the Cyto-Tail of SMO Gene Underlying Isolated Postaxial Polydactyly. Molecular Syndromology 2024, 1-7. DOI: 10.1159/000539279.Peer-Reviewed Original ResearchHomozygous missense variantWhole-exome sequencingHereditary limb malformationsSonic hedgehog pathwayAutosomal recessive mannerSequence variantsMissense variantsProtein foldingIsolated postaxial polydactylyExome sequencingSegregation analysisNovel variantsConsanguineous familySanger sequencingSMO genesExtra digitsHomology modelingCellular differentiationHedgehog pathwayRecessive mannerEmbryonic cellsPostaxial polydactylySequencePreaxial polydactylyVariants
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 membersVariantsExpansion of NEUROD2 phenotypes to include developmental delay without seizures
Mis EK, Sega AG, Signer RH, Cartwright T, Ji W, Martinez‐Agosto J, Nelson SF, Palmer CGS, Lee H, Mitzelfelt T, Konstantino M, Network U, Jeffries L, Khokha MK, Marco E, Martin MG, Lakhani SA. Expansion of NEUROD2 phenotypes to include developmental delay without seizures. American Journal Of Medical Genetics Part A 2021, 185: 1076-1080. PMID: 33438828, PMCID: PMC8212414, DOI: 10.1002/ajmg.a.62064.Peer-Reviewed Original ResearchConceptsDevelopmental delayEarly-onset seizuresDe novo heterozygous variantsNovo heterozygous variantsDifferentiation factor 2Xenopus laevis tadpolesHeterozygous variantsSeizuresNeuronal differentiationParental studiesFunctional testingMissense variantsPatient variantsFunctional evidenceFactor 2Vivo assaysLaevis tadpolesVariant pathogenicityFunction effectsAdolescentsVariants
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 dataSyndromeHypoplasiaIllnessVariantsFindingsNovel compound heterozygous variants in NHLRC2 in a patient with FINCA syndrome
Brodsky NN, Boyarchuk O, Kovalchuk T, Hariyan T, Rice A, Ji W, Khokha M, Lakhani S, Lucas CL. Novel compound heterozygous variants in NHLRC2 in a patient with FINCA syndrome. Journal Of Human Genetics 2020, 65: 911-915. PMID: 32435055, DOI: 10.1038/s10038-020-0776-0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAngiomatosisBrain NeoplasmsCardiomegalyChild, PreschoolExome SequencingFibrosisHeterozygoteHumansIntracellular Signaling Peptides and ProteinsLung DiseasesMaleModels, MolecularNeurodegenerative DiseasesPedigreePoint MutationProtein ConformationProtein DomainsSequence AlignmentSequence Homology, Amino AcidSyndromeConceptsWhole-exome sequencingNovel compound heterozygous variantsCompound heterozygous variantsUkrainian patientsClinical featuresNovel variantsNew patientsHealthy humansCompound heterozygous combinationPatientsHeterozygous variantsSyndromeFinnish childrenNHLRC2Sanger sequencingFibrosisDiseaseGnomAD databaseN-terminal thioredoxinCentral regulatorVariantsNeurodegeneration