2018
Pklr Intron Splicing-Associated Mutations and Alternate Diagnoses Are Common in Pyruvate Kinase Deficient Patients with Single or No Pklr Coding Mutations
Lezon-Geyda K, Rose M, McNaull M, Knoll C, Yaish H, Pastore Y, Fermi E, Glader B, Bianchi P, Grace R, Gallagher P. Pklr Intron Splicing-Associated Mutations and Alternate Diagnoses Are Common in Pyruvate Kinase Deficient Patients with Single or No Pklr Coding Mutations. Blood 2018, 132: 3607. DOI: 10.1182/blood-2018-99-117805.Peer-Reviewed Original ResearchWhole-genome sequencingPyruvate kinase-deficient patientsSplice siteDonor splice sitePyruvate kinasePK-deficient patientsGenome sequencingPKLR geneSequence analysisWhole-exome sequencingIntron mutationsDominant negative phenotypeExon 7Exon 10Detailed sequence analysisPyruvate kinase geneDisease-associated variantsRare genetic variantsNormal mRNA processingSplice acceptor siteRegion mutationsIntron retentionErythroid promoterGenome databasePremature chain termination
2005
A novel splicing mutation of the α-spectrin gene in the original hereditary pyropoikilocytosis kindred
Costa DB, Lozovatsky L, Gallagher PG, Forget BG. A novel splicing mutation of the α-spectrin gene in the original hereditary pyropoikilocytosis kindred. Blood 2005, 106: 4367-4369. PMID: 16150946, PMCID: PMC1895230, DOI: 10.1182/blood-2005-05-1813.Peer-Reviewed Original ResearchConceptsFrame premature termination codonsRed blood cell membrane skeletonCell membrane skeletonΑ-spectrin geneHereditary pyropoikilocytosisPremature termination codonConsensus splice sitesTissue culture cellsNovel splicing mutationMembrane skeletonIntronic fragmentTermination codonGene transcriptsAlpha-spectrinAbnormal splicingSplice siteStructural variantsGene transferMolecular defectsSplicing mutationCulture cellsAllelesExon 22TranscriptsMutations
2004
Sequences Downstream of the Erythroid Promoter Promote High-Level Expression of the Human α-Spectrin Gene by Providing Boundary Activity and Positive Regulatory Elements.
Gallagher P, Nilson D, Lin J, Bodine D. Sequences Downstream of the Erythroid Promoter Promote High-Level Expression of the Human α-Spectrin Gene by Providing Boundary Activity and Positive Regulatory Elements. Blood 2004, 104: 1572. DOI: 10.1182/blood.v104.11.1572.1572.Peer-Reviewed Original ResearchPositive regulatory elementGATA-1 sitesAγ-globin geneRegulatory elementsIntron 1Exon 1Gene expressionLuc activitySplice siteGATA-1 activityErythroid-specific expressionHypersensitive site mappingΒ-globin promoterΑ-spectrin geneK562 cellsTransient transfection assaysMutant exon 1Γ-globin proteinMouse linesHigh-level expressionChromatin modifications
1997
Spectrin St Claude, a Splicing Mutation of the Human α-Spectrin Gene Associated With Severe Poikilocytic Anemia
Fournier C, Nicolas G, Gallagher P, Dhermy D, Grandchamp B, Lecomte M. Spectrin St Claude, a Splicing Mutation of the Human α-Spectrin Gene Associated With Severe Poikilocytic Anemia. Blood 1997, 89: 4584-4590. PMID: 9192783, DOI: 10.1182/blood.v89.12.4584.Peer-Reviewed Original ResearchConceptsAlpha-spectrin chainAcceptor splice siteSplice siteSplicing mutationAlpha-spectrin geneΑ-spectrin geneExon 20New acceptor splice siteMolecular basisTermination codonNovel mRNAInsertion upstreamTract mutationsTryptic digestionMutationsG mutationGenesMRNAHeterozygous parentsErythrocyte membranesMembraneFrame skippingCodonSitesVariants
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