2019
Aberrant splicing contributes to severe α-spectrin-linked congenital hemolytic anemia
Gallagher PG, Maksimova Y, Lezon-Geyda K, Newburger PE, Medeiros D, Hanson RD, Rothman J, Israels S, Wall DA, Sidonio RF, Sieff C, Gowans LK, Mittal N, Rivera-Santiago R, Speicher DW, Baserga SJ, Schulz VP. Aberrant splicing contributes to severe α-spectrin-linked congenital hemolytic anemia. Journal Of Clinical Investigation 2019, 129: 2878-2887. PMID: 31038472, PMCID: PMC6597203, DOI: 10.1172/jci127195.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Hemolytic, CongenitalErythrocyte MembraneFemaleHumansMaleMutation, MissenseRNA Splice SitesRNA SplicingSpectrinConceptsRecessive hereditary spherocytosisSplice acceptor siteHuman genetic diseasesMRNA stability studiesAberrant splicing contributesSplicing contributesWhole-genome sequencingSplicing analysisHereditary pyropoikilocytosisTermination codonNull allelesGenome sequencingWhole-exome sequencingBranch pointsNumerous mutationsGenetic diseasesLinkage disequilibriumMRNA transcriptsΑ-spectrinMinigene studiesAcceptor sitesMutationsExome sequencingNew targets
2017
Hereditary xerocytosis: Diagnostic considerations
Risinger M, Glogowska E, Chonat S, Zhang K, Dagaonkar N, Joiner CH, Quinn CT, Kalfa TA, Gallagher PG. Hereditary xerocytosis: Diagnostic considerations. American Journal Of Hematology 2017, 93: e67-e69. PMID: 29210095, PMCID: PMC5807085, DOI: 10.1002/ajh.24996.Peer-Reviewed Original ResearchNovel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis
Glogowska E, Schneider ER, Maksimova Y, Schulz VP, Lezon-Geyda K, Wu J, Radhakrishnan K, Keel SB, Mahoney D, Freidmann AM, Altura RA, Gracheva EO, Bagriantsev SN, Kalfa TA, Gallagher PG. Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis. Blood 2017, 130: 1845-1856. PMID: 28716860, PMCID: PMC5649553, DOI: 10.1182/blood-2017-05-786004.Peer-Reviewed Original ResearchConceptsHereditary xerocytosisMembrane protein traffickingNext-generation sequencing-based techniquesSequencing-based techniquesMembrane protein expressionProtein traffickingFunction phenotypesCell biologyOsmotic stressWild typePIEZO1 variantsFunctional assaysNovel mechanismGenetic heterogeneityMutationsProtein expressionErythrocyte hydrationXerocytosisVivo systemTraffickingPartial gainPhenotypeChannel inactivationCation permeabilityCongenital hemolytic anemiaHemoglobin C trait accentuates erythrocyte dehydration in hereditary xerocytosis
Yang E, Voelkel EB, Lezon‐Geyda K, Schulz VP, Gallagher PG. Hemoglobin C trait accentuates erythrocyte dehydration in hereditary xerocytosis. Pediatric Blood & Cancer 2017, 64 PMID: 28121068, PMCID: PMC5858911, DOI: 10.1002/pbc.26444.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnemia, Hemolytic, CongenitalErythrocyte IndicesErythrocytesHemoglobin C DiseaseHumansHydrops FetalisIon ChannelsMaleMutationConceptsMean corpuscular hemoglobin concentrationElevated mean corpuscular hemoglobin concentrationHemoglobin C traitErythrocyte dehydrationC traitHereditary xerocytosisCorpuscular hemoglobin concentrationAcute hemolysisHbC traitHemoglobin concentrationEvidence of dehydrationOsmotic gradient ektacytometryPatientsPIEZO1 mutationsEktacytometryGenetic studies
2016
Allogeneic bone marrow transplantation for treatment of severe hemolytic anemia attributable to hexokinase deficiency
Khazal S, Polishchuk V, Manwani D, Gallagher PG, Prinzing S, Mahadeo KM. Allogeneic bone marrow transplantation for treatment of severe hemolytic anemia attributable to hexokinase deficiency. Blood 2016, 128: 735-737. PMID: 27297791, DOI: 10.1182/blood-2016-03-702860.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Hemolytic, CongenitalBase SequenceBone Marrow TransplantationChild, PreschoolDNA Mutational AnalysisHexokinaseHumansMaleMutationSeverity of Illness IndexTransplantation, Homologous
2015
Diagnosis and management of rare congenital nonimmune hemolytic disease.
Gallagher PG. Diagnosis and management of rare congenital nonimmune hemolytic disease. Hematology 2015, 2015: 392-9. PMID: 26637748, DOI: 10.1182/asheducation-2015.1.392.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnemia, Hemolytic, CongenitalChildErythrocytesHematologyHemoglobinopathiesHemoglobinsHemolysisHumansHydrops FetalisMedical OncologyNucleotidesReticulocytesSplenectomyConceptsErythrocyte hydrationHemolytic diseaseErythrocyte metabolismGroup of disordersEpisodic hemolysisLaboratory manifestationsPathophysiologic mechanismsClinical findingsHemolytic anemiaChronic hemolysisHemolytic disordersImportant causeDiseaseHeterogeneous groupDisordersAnemiaErythrocyte structureAbnormalitiesHemoglobin stabilityPathway leadUnstable hemoglobinopathiesMetabolismManagement considerationsUnstable hemoglobinHemolysisMutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis
Glogowska E, Lezon-Geyda K, Maksimova Y, Schulz VP, Gallagher PG. Mutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis. Blood 2015, 126: 1281-1284. PMID: 26198474, PMCID: PMC4566808, DOI: 10.1182/blood-2015-07-657957.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnemia, Hemolytic, CongenitalBase SequenceDNA Mutational AnalysisExomeFemaleGenes, DominantGenetic Association StudiesHeterozygoteHumansHydrops FetalisIntermediate-Conductance Calcium-Activated Potassium ChannelsIon ChannelsMaleMolecular Sequence DataMutation, MissensePedigreeSequence Homology, Amino AcidConceptsErythrocyte volume homeostasisAutosomal dominant hemolytic anemiaPotassium channel proteinHereditary xerocytosisHeterozygous mutationsChannel proteinsWhole-exome sequencingKCNN4 geneSame residuesSegregation analysisDisease phenotypeMutationsCellular dehydrationChannel mutationsGardos channelHX patientsDifferent mutationsCritical rolePiezo1XerocytosisWater lossVolume homeostasisChannel inactivationRecent studiesDeoxy conditions
2014
Piezo Proteins: Regulators of Mechanosensation and Other Cellular Processes*
Bagriantsev SN, Gracheva EO, Gallagher PG. Piezo Proteins: Regulators of Mechanosensation and Other Cellular Processes*. Journal Of Biological Chemistry 2014, 289: 31673-31681. PMID: 25305018, PMCID: PMC4231648, DOI: 10.1074/jbc.r114.612697.Peer-Reviewed Original ResearchConceptsPiezo proteinsCellular processesMammalian cellsCellular developmentMechanosensory transductionCellular migrationIon channelsHereditary xerocytosisVolume regulationProteinBiologic processesRegulationImportant insightsTransductionMechanosensationRegulatorMutationsXerocytosisProliferationCellsMechanoVariety of disordersElongationMigrationProminent feature
2013
Abnormalities of the Erythrocyte Membrane
Gallagher PG. Abnormalities of the Erythrocyte Membrane. Pediatric Clinics Of North America 2013, 60: 1349-1362. PMID: 24237975, PMCID: PMC4155395, DOI: 10.1016/j.pcl.2013.09.001.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Hemolytic, CongenitalElliptocytosis, HereditaryErythrocyte MembraneErythrocytesHumansSpherocytosis, HereditarySplenectomyConceptsCommon primary disordersRole of splenectomyHealth care providersLong-term riskMost patientsSymptomatic anemiaPrimary disorderCare providersPrimary abnormalitySplenectomyPatientsManagement guidelinesHereditary spherocytosisHereditary spherocytosis patientsErythrocyte membranesAbnormalitiesGenetic heterogeneityAnemiaSyndromeTherapy
2012
Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis
Zarychanski R, Schulz VP, Houston BL, Maksimova Y, Houston DS, Smith B, Rinehart J, Gallagher PG. Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis. Blood 2012, 120: 1908-1915. PMID: 22529292, PMCID: PMC3448561, DOI: 10.1182/blood-2012-04-422253.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnemia, Hemolytic, CongenitalBase SequenceDNA Mutational AnalysisErythroid CellsExomeFamily HealthFemaleGene ExpressionGenetic Predisposition to DiseaseGenotypeHumansHydrops FetalisIon ChannelsMaleMass SpectrometryMechanotransduction, CellularMolecular Sequence DataMutationPedigreeProteomicsReverse Transcriptase Polymerase Chain ReactionConceptsPiezo proteinsErythrocyte volume homeostasisAutosomal dominant hemolytic anemiaHereditary xerocytosisPiezo familyMammalian cellsTransduction channelsCell mRNADiscovery proteomicsPIEZO1 mutationsGenetic diseasesSegregation analysisDisease phenotypeMutationsLinkage studiesHuman erythrocyte membranesProteinExome sequencingNumber analysisNovel mutationsPiezo1DNA levelsXerocytosisFirst reportVolume homeostasis
2011
Refinement of the hereditary xerocytosis locus on chromosome 16q in a large Canadian kindred
Houston BL, Zelinski T, Israels SJ, Coghlan G, Chodirker BN, Gallagher PG, Houston DS, Zarychanski R. Refinement of the hereditary xerocytosis locus on chromosome 16q in a large Canadian kindred. Blood Cells Molecules And Diseases 2011, 47: 226-231. PMID: 21944700, DOI: 10.1016/j.bcmd.2011.08.001.Peer-Reviewed Original ResearchConceptsNormal hemoglobin levelsLarge CanadianProgressive iron loadingRed cell hemolysisCausative genetic mutationsHemoglobin levelsIndirect hyperbilirubinemiaAffected family membersClinical hallmarkHereditary xerocytosisMorphologic evaluationHemolytic processChromosome 16qTarget cellsOsmotic fragilityPhenotypic findingsGenetic mutationsDisease phenotypeCell hemolysisIron loadingFamily membersMode of inheritanceHemolysisHeterogeneous conditionCholelithiasis
2009
The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes
Stewart AK, Vandorpe DH, Heneghan JF, Chebib F, Stolpe K, Akhavein A, Edelman EJ, Maksimova Y, Gallagher PG, Alper SL. The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes. American Journal Of Physiology - Cell Physiology 2009, 298: c283-c297. PMID: 19907019, PMCID: PMC2822494, DOI: 10.1152/ajpcell.00444.2009.Peer-Reviewed Original Research4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAmbystoma mexicanumAmino Acid SequenceAmphibiansAnemia, Hemolytic, CongenitalAnimalsAnion Exchange Protein 1, ErythrocyteBicarbonatesBumetanideCell MembraneCell Membrane PermeabilityChloridesCloning, MolecularDNA Mutational AnalysisFemaleGlycophorinsHeterozygoteHumansHydrogen-Ion ConcentrationKineticsMaleMembrane PotentialsMiddle AgedMolecular Sequence DataMutation, MissenseOocytesOuabainOxalic AcidRubidium RadioisotopesSeverity of Illness IndexSodium Potassium Chloride Symporter InhibitorsSodium-Potassium-Exchanging ATPaseSulfatesXenopus laevis
2008
Structural and functional effects of hereditary hemolytic anemia-associated point mutations in the alpha spectrin tetramer site
Gaetani M, Mootien S, Harper S, Gallagher PG, Speicher DW. Structural and functional effects of hereditary hemolytic anemia-associated point mutations in the alpha spectrin tetramer site. Blood 2008, 111: 5712-5720. PMID: 18218854, PMCID: PMC2424163, DOI: 10.1182/blood-2007-11-122457.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnemia, Hemolytic, CongenitalBinding SitesCalorimetry, Differential ScanningCircular DichroismEntropyErythrocytesGene ExpressionGenotypeHumansMolecular Sequence DataPhenotypePoint MutationProtein BindingRecombinant ProteinsSpectrinSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationStructure-Activity Relationship
2005
Red Cell Membrane Disorders
Gallagher PG. Red Cell Membrane Disorders. Hematology 2005, 2005: 13-18. PMID: 16304353, DOI: 10.1182/asheducation-2005.1.13.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, HemolyticAnemia, Hemolytic, CongenitalCardiovascular DiseasesElliptocytosis, HereditaryErythrocyte MembraneHumansMembrane ProteinsSpherocytosis, HereditarySplenectomyConceptsComplications of splenectomyOverwhelming postsplenectomy infectionRecent management guidelinesRole of splenectomyPenicillin-resistant pneumococciHealth care providersLong-term riskPulmonary hypertensionLaparoscopic approachMost patientsPostsplenectomy infectionSurgical methodsLaboratory heterogeneityCardiovascular diseaseHemolytic anemiaCare providersSplenectomyThrombotic disordersManagement guidelinesHereditary spherocytosisDisordersInfectionPrivate mutationsRed cell membrane disordersSpherocytosis
2004
Update on the clinical spectrum and genetics of red blood cell membrane disorders.
Gallagher PG. Update on the clinical spectrum and genetics of red blood cell membrane disorders. Current Hematology Reports 2004, 3: 85-91. PMID: 14965483.Peer-Reviewed Original ResearchConceptsStructure/function relationshipsSignificant genetic heterogeneityPrecise genetic defectGenetic lociMolecular biologyRed blood cell membrane disordersSplicing mutationGene deletionNonsense mutationCell membraneFunction relationshipsGenetic heterogeneityGenetic defectsHereditary elliptocytosisMembrane disordersRed blood cell membraneBlood cell membranesHereditary pyropoikilocytosisMutationsBetter understandingErythrocyte membranesMembraneLociGeneticsBiology
2003
Altered erythrocyte endothelial adherence and membrane phospholipid asymmetry in hereditary hydrocytosis
Gallagher PG, Chang SH, Rettig MP, Neely JE, Hillery CA, Smith BD, Low PS. Altered erythrocyte endothelial adherence and membrane phospholipid asymmetry in hereditary hydrocytosis. Blood 2003, 101: 4625-4627. PMID: 12560240, DOI: 10.1182/blood-2001-12-0329.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnemia, Hemolytic, CongenitalCase-Control StudiesCell AdhesionChildEndothelium, VascularErythrocyte MembraneErythrocytesFamily HealthHumansMalePhosphatidylserinesThrombosisUmbilical VeinsConceptsMechanism of thrombosisErythrocyte filtration rateSickle cell diseaseAdherence of erythrocytesMembrane phospholipid asymmetryAdhesion of erythrocytesFiltration rateHealthy controlsCell diseaseUncommon variantEndothelial adherenceMild increaseThrombosisPatientsEndothelial monolayersPhosphatidylserine exposureErythrocytesPhospholipid asymmetryAdherenceHereditary stomatocytosisDisease
1997
Mutation of a highly conserved residue of betaI spectrin associated with fatal and near-fatal neonatal hemolytic anemia.
Gallagher PG, Petruzzi MJ, Weed SA, Zhang Z, Marchesi SL, Mohandas N, Morrow JS, Forget BG. Mutation of a highly conserved residue of betaI spectrin associated with fatal and near-fatal neonatal hemolytic anemia. Journal Of Clinical Investigation 1997, 99: 267-277. PMID: 9005995, PMCID: PMC507794, DOI: 10.1172/jci119155.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Hemolytic, CongenitalArginineBase SequenceConserved SequenceErythrocyte MembraneFemaleHomozygoteHumansHydrops FetalisLaosLeucineMaleMembrane ProteinsModels, MolecularMuscle, SkeletalPedigreePeptide MappingPoint MutationPolymerase Chain ReactionProtein ConformationSequence Analysis, DNASpectrinConceptsImportance of leucineEvolutionary conservationSpectrin functionSpectrin repeatsBeta spectrinBetaI spectrinTriple helical modelGenetic studiesSpectrinMutationsSkeletal muscleMolecular modelingTriple helixNormal functionHelical modelLeucineErythrocyte membranesDrosophilaHydrophobic interactionsNeonatal hemolytic anemiaRepeatsHelixConservationResiduesMembrane
1996
Molecular basis and haplotyping of the alphaII domain polymorphisms of spectrin: application to the study of hereditary elliptocytosis and pyropoikilocytosis.
Gallagher PG, Kotula L, Wang Y, Marchesi SL, Curtis PJ, Speicher DW, Forget BG. Molecular basis and haplotyping of the alphaII domain polymorphisms of spectrin: application to the study of hereditary elliptocytosis and pyropoikilocytosis. American Journal Of Human Genetics 1996, 59: 351-9. PMID: 8755921, PMCID: PMC1914747.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnemia, Hemolytic, CongenitalAsianAsian PeopleBase SequenceBiological EvolutionBlack PeopleElliptocytosis, HereditaryErythrocytes, AbnormalHaplotypesHumansModels, GeneticMolecular Sequence DataMutagenesis, InsertionalPolymorphism, GeneticPrevalenceRepetitive Sequences, Nucleic AcidSpectrinUnited StatesWhite PeopleConceptsAlpha-spectrin geneAmino acid sequenceAcid sequenceHereditary elliptocytosisAlpha-spectrin chainHereditary pyropoikilocytosisPrincipal structural proteinErythrocyte membrane skeletonSingle nucleotide substitutionEvolutionary originLimited tryptic digestionMembrane skeletonMolecular basisGenomic DNANucleotide substitutionsStructural proteinsAlpha-spectrinDifferent haplotypesFounder effectGenesLinkage disequilibriumOnly haplotypeSpectrin proteinsCommon haplotypeTryptic digestion
1992
A common type of the spectrin alpha I 46-50a-kD peptide abnormality in hereditary elliptocytosis and pyropoikilocytosis is associated with a mutation distant from the proteolytic cleavage site. Evidence for the functional importance of the triple helical model of spectrin.
Gallagher PG, Tse WT, Coetzer T, Lecomte MC, Garbarz M, Zarkowsky HS, Baruchel A, Ballas SK, Dhermy D, Palek J. A common type of the spectrin alpha I 46-50a-kD peptide abnormality in hereditary elliptocytosis and pyropoikilocytosis is associated with a mutation distant from the proteolytic cleavage site. Evidence for the functional importance of the triple helical model of spectrin. Journal Of Clinical Investigation 1992, 89: 892-898. PMID: 1541680, PMCID: PMC442935, DOI: 10.1172/jci115669.Peer-Reviewed Original ResearchConceptsProteolytic cleavage sitesAlpha-spectrin chainTriple helical modelCleavage siteHelix 2Helix-breaking proline substitutionsHereditary elliptocytosisAlpha iAlpha-spectrin geneAlpha-helical structureAmino-terminal sideHereditary pyropoikilocytosisHelical modelErythrocyte membrane proteinsLimited tryptic digestionMembrane proteinsSpectrin repeatsDNA sequencesSpectrin chainsHelix 3Position 207Leucine residuesFunctional importanceProline substitutionPoint mutations