2020
Genetic pathways disrupted by ENPP1 deficiency provide insight into mechanisms of osteoporosis, osteomalacia, and paradoxical mineralization
Maulding ND, Kavanagh D, Zimmerman K, Coppola G, Carpenter TO, Jue NK, Braddock DT. Genetic pathways disrupted by ENPP1 deficiency provide insight into mechanisms of osteoporosis, osteomalacia, and paradoxical mineralization. Bone 2020, 142: 115656. PMID: 32980560, PMCID: PMC7744330, DOI: 10.1016/j.bone.2020.115656.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFibroblast Growth Factor-23MiceOsteomalaciaOsteoporosisPhosphoric Diester HydrolasesPhosphoric Monoester HydrolasesPyrophosphatasesVascular CalcificationConceptsGenetic pathwaysSkeletal phenotypeGene expressionHuman disease phenotypesAsj/Suppression of WntTranscript countsGene transcriptionENPP1-deficient miceGene pathwaysEnzyme functionENPP1 deficiencyWnt ligandsSoluble Wnt inhibitorsWnt activityReduced gene transcriptionBiomechanical phenotypeTranscriptionWnt inhibitorsBone findingsUnbiased analysisDisease phenotypePhenotypeOld miceStrong signature
2019
Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations
Kotwal A, Ferrer A, Kumar R, Singh RJ, Murthy V, Schultz-Rogers L, Zimmermann M, Lanpher B, Zimmerman K, Stabach PR, Klee E, Braddock DT, Wermers RA. Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations. Journal Of Bone And Mineral Research 2019, 35: 662-670. PMID: 31826312, PMCID: PMC7771569, DOI: 10.1002/jbmr.3938.Peer-Reviewed Original ResearchMeSH KeywordsAdultCarotid Intima-Media ThicknessFemaleFibroblast Growth Factor-23HumansMiddle AgedMutationPhenotypePhosphoric Diester HydrolasesPyrophosphatasesConceptsAutosomal recessive hypophosphatemic rickets type 2Biallelic mutationsMonoallelic mutationsPrimary hyperparathyroidismPathogenic variantsCarotid intima-media thicknessClassic disease manifestationsNormocalcemic primary hyperparathyroidismC-terminal FGF23Intima-media thicknessWhole-exome sequencingClinical findingsArterial calcificationPeriarticular calcificationSpectrum of phenotypesIntact FGF23Disease manifestationsBilateral femursENPP1 variantsBone deformitiesBiochemical manifestationsType 2ENPP1 geneExome sequencingHyperparathyroidismHuman Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency
Oheim R, Zimmerman K, Maulding ND, Stürznickel J, von Kroge S, Kavanagh D, Stabach PR, Kornak U, Tommasini SM, Horowitz MC, Amling M, Thompson D, Schinke T, Busse B, Carpenter TO, Braddock DT. Human Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency. Journal Of Bone And Mineral Research 2019, 35: 528-539. PMID: 31805212, PMCID: PMC7184798, DOI: 10.1002/jbmr.3911.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsFamilial Hypophosphatemic RicketsFibroblast Growth Factor-23Fibroblast Growth FactorsHumansMaleMiceOsteoporosisPhenotypePhosphoric Diester HydrolasesPyrophosphatasesConceptsAutosomal recessive hypophosphatemic rickets type 2ENPP1 deficiencyEarly-onset osteoporosisGene-dose effectOnset osteoporosisAsj/Bone mineral density scansBone mineralization disturbancesRenal phosphate wastingCortical boneDose effectMild osteomalaciaMineralization disturbancesFGF23 levelsMild elevationPlasma FGF23Arterial calcificationBone massPhosphate wastingSkeletal manifestationsBone fragilityThoracic spineWild-type family membersType 2Adult menExtraskeletal Calcifications in Hutchinson-Gilford Progeria Syndrome
Gordon C, Cleveland R, Baltrusaitis K, Massaro J, D'Agostino R, Liang M, Snyder B, Walters M, Li X, Braddock D, Kleinman M, Kieran M, Gordon L. Extraskeletal Calcifications in Hutchinson-Gilford Progeria Syndrome. Bone 2019, 125: 103-111. PMID: 31077852, PMCID: PMC6628204, DOI: 10.1016/j.bone.2019.05.008.Peer-Reviewed Original ResearchConceptsUrinary calcium/creatinine ratioCalcium/creatinine ratioExtraskeletal calcificationParathyroid hormoneClinical trialsHutchinson-Gilford progeria syndromeCreatinine ratioPhysical examinationNormal limitsPlasma magnesiumFibroblast growth factor 23Successive clinical trialsNormal renal functionCalcium carbonate supplementationGrowth factor 23Age-matched controlsEvaluable patientsRoutine supplementationSupplement discontinuationZoledronate therapyRenal functionCalcinosis cutisCalcium supplementationFactor 23Serum calcium