2020
Genotype‐phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency
Bianchi P, Fermo E, Lezon‐Geyda K, van Beers E, Morton HD, Barcellini W, Glader B, Chonat S, Ravindranath Y, Newburger PE, Kollmar N, Despotovic JM, Verhovsek M, Sharma M, Kwiatkowski JL, Kuo KHM, Wlodarski MW, Yaish HM, Holzhauer S, Wang H, Kunz J, Addonizio K, Al‐Sayegh H, London WB, Andres O, van Wijk R, Gallagher PG, Grace RFF. Genotype‐phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency. American Journal Of Hematology 2020, 95: 472-482. PMID: 32043619, PMCID: PMC8127999, DOI: 10.1002/ajh.25753.Peer-Reviewed Original ResearchConceptsNon-missense mutationsPyruvate kinase deficiencyRare severe complicationsFrequency of complicationsLower extremity ulcerationsLower hemoglobin levelsKinase deficiencyNatural history studiesDifferent pathogenic variantsTerms of hemoglobinCongenital hemolytic anemiaGenotype-phenotype correlationLifetime transfusionsDeficient womenPregnancy outcomesPulmonary hypertensionSevere complicationsSplenectomy statusHemoglobin levelsHepatic failureNewborn periodClinical similaritiesWide genetic heterogeneityIron overloadHemolytic anemia
2018
Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study
Grace RF, Bianchi P, van Beers EJ, Eber SW, Glader B, Yaish HM, Despotovic JM, Rothman JA, Sharma M, McNaull MM, Fermo E, Lezon-Geyda K, Morton DH, Neufeld EJ, Chonat S, Kollmar N, Knoll CM, Kuo K, Kwiatkowski JL, Pospíšilová D, Pastore YD, Thompson AA, Newburger PE, Ravindranath Y, Wang WC, Wlodarski MW, Wang H, Holzhauer S, Breakey VR, Kunz J, Sheth S, Rose MJ, Bradeen HA, Neu N, Guo D, Al-Sayegh H, London WB, Gallagher PG, Zanella A, Barcellini W. Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study. Blood 2018, 131: 2183-2192. PMID: 29549173, DOI: 10.1182/blood-2017-10-810796.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnemia, Hemolytic, Congenital NonspherocyticBlood TransfusionChildChild, PreschoolCholecystectomyCombined Modality TherapyEnzyme ActivationFemaleGenetic Association StudiesGenotypeHumansInfantInfant, NewbornMaleMiddle AgedMutationPhenotypePyruvate KinasePyruvate Metabolism, Inborn ErrorsSplenectomySymptom AssessmentTreatment OutcomeYoung AdultConceptsIron overloadHemolytic anemiaPyruvate kinase deficiencyChildren age 5 yearsProspective clinical dataPK deficiencySeverity of anemiaKinase deficiencyNatural history studiesAge 5 yearsCongenital nonspherocytic hemolytic anemiaCongenital hemolytic anemiaBaseline hemoglobinPostsplenectomy thrombosisMulticenter registryPostsplenectomy sepsisPulmonary hypertensionSimultaneous cholecystectomyFrequent complicationPerinatal complicationsTransfusion burdenAplastic crisisExchange transfusionLeg ulcersRadiologic data
2017
Novel 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 anemia