2013
The 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
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 RelationshipConceptsObserved clinical symptomsClinical symptomsCommon hereditary elliptocytosisPathogenic mutationsHereditary elliptocytosisFunctional effects
2007
Identification and Characterization of α-Spectrin Mutations Associated with Inherited Hemolytic Anemia.
Tolpinrud W, Gaetani M, Maksimova Y, Mootien S, Harper S, Forget B, Speicher D, Gallagher P. Identification and Characterization of α-Spectrin Mutations Associated with Inherited Hemolytic Anemia. Blood 2007, 110: 1706. DOI: 10.1182/blood.v110.11.1706.1706.Peer-Reviewed Original ResearchWild typeMissense mutationsSelf-association siteMembrane skeletonΑ-spectrinHereditary elliptocytosisProline substitutionSpectrin peptidesHereditary pyropoikilocytosisCommon protein polymorphismHPLC gel filtrationHuman disease pathogenesisCharacterization of variantsErythrocyte membrane skeletonMajor structural componentTriple-helical configurationMembrane biologyDifferent missense mutationsSpectrin gene
2004
A Position +5 Intronic Mutation in the α-Spectrin Gene Is Associated with Marked Deficiency of α-Spectrin Production in the First Reported Cases of Hereditary Pyropoikilocytosis.
Costa D, Gallagher P, Forget B. A Position +5 Intronic Mutation in the α-Spectrin Gene Is Associated with Marked Deficiency of α-Spectrin Production in the First Reported Cases of Hereditary Pyropoikilocytosis. Blood 2004, 104: 576. DOI: 10.1182/blood.v104.11.576.576.Peer-Reviewed Original ResearchHereditary 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 membranesMembraneLociGeneticsBiology
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 ResearchConceptsGenetic basisHereditary elliptocytosisHereditary pyropoikilocytosisDistinct haplotypesGenetic analysisProtein phenotypeAlpha-spectrinChromosomal backgroundΑI domainSpectrinPolymorphismMutationsHaplotypesPhenotypeElliptocytosisPyropoikilocytosisPCRAssaysFamilyGene polymorphismsDomainIdentification
1996
Epidemiological 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 ResearchConceptsHereditary 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 Research
1993
Poikilocytic hereditary elliptocytosis associated with spectrin Alexandria: an alpha I/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 alpha I/50b Kd variant that is caused by a single amino acid deletion. Blood 1993, 82: 2210-2215. DOI: 10.1182/blood.v82.7.2210.bloodjournal8272210.Peer-Reviewed Original ResearchRed 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 analysisIndividualsPoikilocytic 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
1991
Spectrin Rouen (beta 220-218), a novel shortened beta-chain variant in a kindred with hereditary elliptocytosis. Characterization of the molecular defect as exon skipping due to a splice site mutation.
Garbarz M, Tse WT, Gallagher PG, Picat C, Lecomte MC, Galibert F, Dhermy D, Forget BG. Spectrin Rouen (beta 220-218), a novel shortened beta-chain variant in a kindred with hereditary elliptocytosis. Characterization of the molecular defect as exon skipping due to a splice site mutation. Journal Of Clinical Investigation 1991, 88: 76-81. PMID: 2056132, PMCID: PMC296005, DOI: 10.1172/jci115307.Peer-Reviewed Original ResearchConceptsBeta-spectrin chainBeta-spectrin geneCDNA amplification productsAmino acidsExon YGenomic DNANucleotide sequencingExample of exonMolecular defectsAnalysis of cDNAAmplification productsHereditary elliptocytosisConsensus splice sitesNovel amino acidCarboxy terminusIntron downstreamSplice siteSplice site mutationSouthern blotExonsExon skipReticulocyte RNACDNAPenultimate exonSite mutation