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 heterogeneityAnemiaSyndromeTherapyThe common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation
Harper SL, Sriswasdi S, Tang HY, Gaetani M, Gallagher PG, Speicher DW. The common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation. Blood 2013, 122: 3045-3053. PMID: 23974198, PMCID: PMC3811177, DOI: 10.1182/blood-2013-02-487702.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBinding SitesCross-Linking ReagentsElliptocytosis, HereditaryErythrocyte MembraneHumansModels, MolecularMolecular Sequence DataMutationProtein BindingProtein MultimerizationProtein StabilityProtein Structure, SecondaryProtein Structure, TertiaryRecombinant ProteinsSpectrinConceptsHereditary elliptocytosisMembrane destabilizationLarge conformational rearrangementsGel filtration analysisMembrane proteinsTetramer assemblyHereditary pyropoikilocytosisBiophysical analysisCommon hereditary elliptocytosisConformational rearrangementsDimer conformationHelical contentTetramerization siteFiltration analysisSpectrin tetramersNovel mechanismUnknown mechanismMutationsBinding assaysSpectrinChemical crosslinkingErythrocyte shapeTetramerErythrocyte membranesMembrane
2009
Imaging of the diffusion of single band 3 molecules on normal and mutant erythrocytes
Kodippili GC, Spector J, Sullivan C, Kuypers FA, Labotka R, Gallagher PG, Ritchie K, Low PS. Imaging of the diffusion of single band 3 molecules on normal and mutant erythrocytes. Blood 2009, 113: 6237-6245. PMID: 19369229, PMCID: PMC2699255, DOI: 10.1182/blood-2009-02-205450.Peer-Reviewed Original ResearchMeSH KeywordsAnion Exchange Protein 1, ErythrocyteDiffusionElliptocytosis, HereditaryErythrocyte MembraneHumansSpherocytosis, HereditaryConceptsBand 3 moleculesBand 3Membrane componentsPeripheral membrane proteinsMembrane-spanning proteinsProtein-protein interactionsBand 3 populationMembrane proteinsSingle-particle trackingIntact human erythrocytesPlasma membraneIntact normal erythrocytesRed cell pathologyMotile propertiesDiseased cellsHuman erythrocyte membranesMutant erythrocytesCell pathologyProteinEntire complexHuman erythrocytesCompartment sizeErythrocyte membranesMembraneMembrane abnormalitiesCanine elliptocytosis due to a mutant β‐spectrin
Di Terlizzi R, Gallagher PG, Mohandas N, Steiner LA, Dolce KS, Guo X, Wilkerson MJ, Stockham SL. Canine elliptocytosis due to a mutant β‐spectrin. Veterinary Clinical Pathology 2009, 38: 52-58. PMID: 19228356, DOI: 10.1111/j.1939-165x.2008.00092.x.Peer-Reviewed Original Research
2008
Nonsense mutations of the α-spectrin gene in hereditary pyropoikilocytosis
Tolpinrud W, Maksimova YD, Forget BG, Gallagher PG. Nonsense mutations of the α-spectrin gene in hereditary pyropoikilocytosis. Haematologica 2008, 93: 1752-1754. PMID: 18815189, DOI: 10.3324/haematol.13639.Peer-Reviewed Original Research
2006
Pathogenic proline mutation in the linker between spectrin repeats: disease caused by spectrin unfolding
Johnson CP, Gaetani M, Ortiz V, Bhasin N, Harper S, Gallagher PG, Speicher DW, Discher DE. Pathogenic proline mutation in the linker between spectrin repeats: disease caused by spectrin unfolding. Blood 2006, 109: 3538-3543. PMID: 17192394, PMCID: PMC1852230, DOI: 10.1182/blood-2006-07-038588.Peer-Reviewed Original ResearchElliptocytosis, HereditaryHumansMutation, MissenseProlineProtein FoldingSpectrinSpherocytosis, Hereditary
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
Hereditary elliptocytosis: spectrin and protein 4.1R
Gallagher PG. Hereditary elliptocytosis: spectrin and protein 4.1R. Seminars In Hematology 2004, 41: 142-164. PMID: 15071791, DOI: 10.1053/j.seminhematol.2004.01.003.Peer-Reviewed Original ResearchUpdate 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 membranesMembraneLociGeneticsBiologyMutation of a highly conserved isoleucine disrupts hydrophobic interactions in the αβ spectrin self-association binding site
Gallagher PG, Zhang Z, Morrow JS, Forget BG. Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the αβ spectrin self-association binding site. Laboratory Investigation 2004, 84: 229-234. PMID: 14661034, DOI: 10.1038/labinvest.3700029.Peer-Reviewed Original ResearchConceptsBinding sitesAlpha-spectrin mutationsEvolutionary conservationSpectrin functionSpectrin repeatsTriple helical modelAlpha-spectrinGenetic studiesHydrophobic isoleucineHydrophobic interactionsLow-expression alleleMolecular modelingExpression alleleSpectrinFunctional defectsTriple helixMutationsHelical modelIsoleucineErythrocyte membranesDrosophilaClinical phenotypeNeonatal hemolytic anemiaRepeatsHelix
2003
Hereditary pyropoikilocytosis and the spectrinSt. Claude allele
Mootien S, Gallagher PG. Hereditary pyropoikilocytosis and the spectrinSt. Claude allele. British Journal Of Haematology 2003, 124: 251-252. PMID: 14687038, DOI: 10.1046/j.1365-2141.2003.04748.x.Peer-Reviewed Original ResearchBlack or African AmericanElliptocytosis, HereditaryHumansMutationPassive Cutaneous AnaphylaxisSpectrin
2001
Dynamic molecular modeling of pathogenic mutations in the spectrin self-association domain
Zhang Z, Weed S, Gallagher P, Morrow J. Dynamic molecular modeling of pathogenic mutations in the spectrin self-association domain. Blood 2001, 98: 1645-1653. PMID: 11535493, DOI: 10.1182/blood.v98.6.1645.Peer-Reviewed Original ResearchConceptsSelf-association domainPoint mutationsHuman sequenceDrosophila alpha-spectrinDynamic molecular modelingHuman erythrocyte spectrinCytoskeletal functionSpecific point mutationsConservative substitutionsPrimary sequenceConformational rearrangementsAlpha-spectrinHelical regionHydrophilic residuesAmino acidsMutationsSpectrinSalt bridgeErythrocyte spectrinStructural consequencesPathogenic mutationsRepeat unitsMolecular modelingSequenceStructural disruptionSpectrin Oligomerization is Cooperatively Coupled to Membrane Assembly: A Linkage Targeted by Many Hereditary Hemolytic Anemias?
Giorgi M, Cianci C, Gallagher P, Morrow J. Spectrin Oligomerization is Cooperatively Coupled to Membrane Assembly: A Linkage Targeted by Many Hereditary Hemolytic Anemias? Experimental And Molecular Pathology 2001, 70: 215-230. PMID: 11418000, DOI: 10.1006/exmp.2001.2377.Peer-Reviewed Original Research
1997
Genetic basis of the polymorphisms of the αI domain of spectrin
Gallagher P, Romana M, Wong C, Forget B. Genetic basis of the polymorphisms of the αI domain of spectrin. American Journal Of Hematology 1997, 56: 107-111. PMID: 9326352, DOI: 10.1002/(sici)1096-8652(199710)56:2<107::aid-ajh6>3.0.co;2-2.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnemia, Hemolytic, CongenitalBase SequenceElliptocytosis, HereditaryHaplotypesHumansMutationPolymerase Chain ReactionPolymorphism, GeneticSpectrinConceptsGenetic basisHereditary elliptocytosisHereditary pyropoikilocytosisDistinct haplotypesGenetic analysisProtein phenotypeAlpha-spectrinChromosomal backgroundΑI domainSpectrinPolymorphismMutationsHaplotypesPhenotypeElliptocytosisPyropoikilocytosisPCRAssaysFamilyGene polymorphismsDomainIdentification
1996
Hematologically Important Mutations: Spectrin Variants in Hereditary Elliptocytosis and Hereditary Pyropoikilocytosis
Gallagher P, Forget B. Hematologically Important Mutations: Spectrin Variants in Hereditary Elliptocytosis and Hereditary Pyropoikilocytosis. Blood Cells Molecules And Diseases 1996, 22: 254-258. PMID: 9075575, DOI: 10.1006/bcmd.1996.0105.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Hemolytic, CongenitalElliptocytosis, HereditaryErythrocytes, AbnormalHumansMolecular Sequence DataMutagenesisSpectrinConceptsSpectrin variantEpidemiological studies of spectrin mutations related to hereditary elliptocytosis and spectrin polymorphisms in Benin
Glele‐Kakai C, Garbarz M, Lecomte M, Leborgne S, Galand C, Bournier O, Devaux I, Gautero H, Zohoun I, Gallagher P, Forget B, Dhermy D. Epidemiological studies of spectrin mutations related to hereditary elliptocytosis and spectrin polymorphisms in Benin. British Journal Of Haematology 1996, 95: 57-66. PMID: 8857939, DOI: 10.1046/j.1365-2141.1996.d01-1869.x.Peer-Reviewed Original ResearchMeSH KeywordsBeninElliptocytosis, HereditaryGenetic TestingHumansMutationPoint MutationPolymerase Chain ReactionPolymorphism, GeneticSpectrinConceptsHereditary elliptocytosisGenetic backgroundAlpha-spectrin geneSeparate genetic backgroundsNumber of polymorphismsErythrocyte alpha-spectrinGenetic basisProtein polymorphismsAfrican populationsAlpha-spectrinSpectrin mutationsMolecular defectsMutationsNovel mutationsPolymorphismEpidemiological studiesHE individualsElliptocytosisTwo-thirdsGenesSpectrinPopulationHigh frequencyMolecular 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
1994
Location and PCR‐based detection of three polymorphisms of the human erythrocyte β‐spectrin gene (SPTB)
Gallagher P, Lecomte M, Galand C, Wang Y, Tse W, Forget B. Location and PCR‐based detection of three polymorphisms of the human erythrocyte β‐spectrin gene (SPTB). British Journal Of Haematology 1994, 88: 413-414. PMID: 7803294, DOI: 10.1111/j.1365-2141.1994.tb05043.x.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBase SequenceElliptocytosis, HereditaryHumansMolecular Sequence DataPolymerase Chain ReactionPolymorphism, GeneticSpectrinSpherocytosis, Hereditary
1993
Poikilocytic Hereditary Elliptocytosis Associated With Spectrin Alexandria: An al/50b Kd Variant That Is Caused by a Single Amino Acid Deletion
Gallagher P, Roberts W, Benoit L, Speicher D, Marchesi S, Forget B. Poikilocytic Hereditary Elliptocytosis Associated With Spectrin Alexandria: An al/50b Kd Variant That Is Caused by a Single Amino Acid Deletion. Blood 1993, 82: 2210-2215. PMID: 8400271, DOI: 10.1182/blood.v82.7.2210.2210.Peer-Reviewed Original ResearchConceptsRed blood cellsHereditary elliptocytosisPolymerase chain reactionHeterogeneous disorderBlood cellsSingle amino acid deletionImpaired abilityDifferent severityChain reactionKD variantAffected individualsAlpha iAbnormal peptideAmino acid deletionSpectrin dimer self-associationProteolytic cleavage sitesResidues 470KD peptidePosition 470Limited tryptic digestionAcid deletionProteolytic cleavageErythrocyte membranesAmino acid sequence analysisIndividuals
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