Severe vascular calcification and tumoral calcinosis in a family with hyperphosphatemia: a fibroblast growth factor 23 mutation identified by exome sequencing

dc.contributor.authorShah, Anuja
dc.contributor.authorMiller, Clinton J.
dc.contributor.authorNast, Cynthia C.
dc.contributor.authorAdams, Mark D.
dc.contributor.authorTruitt, Barbara
dc.contributor.authorTayek, John A.
dc.contributor.authorTong, Lili
dc.contributor.authorMehtani, Parag
dc.contributor.authorMonteon, Francisco
dc.contributor.authorSedor, John R.
dc.contributor.authorClinkenbeard, Erica L.
dc.contributor.authorWhite, Kenneth
dc.contributor.authorMehrotra, Rajnish
dc.contributor.authorLaPage, Janine
dc.contributor.authorDickson, Patricia
dc.contributor.authorAdler, Sharon G.
dc.contributor.authorIyengar, Sudha K.
dc.contributor.departmentDepartment of Medical & Molecular Genetics, IU School of Medicineen_US
dc.date.accessioned2016-11-18T18:58:15Z
dc.date.available2016-11-18T18:58:15Z
dc.date.issued2014-12
dc.description.abstractBACKGROUND: Tumoral calcinosis is an autosomal recessive disorder characterized by ectopic calcification and hyperphosphatemia. METHODS: We describe a family with tumoral calcinosis requiring amputations. The predominant metabolic anomaly identified in three affected family members was hyperphosphatemia. Biochemical and phenotypic analysis of 13 kindred members, together with exome analysis of 6 members, was performed. RESULTS: We identified a novel Q67K mutation in fibroblast growth factor 23 (FGF23), segregating with a null (deletion) allele on the other FGF23 homologue in three affected members. Affected siblings had high circulating plasma C-terminal FGF23 levels, but undetectable intact FGF23 or N-terminal FGF23, leading to loss of FGF23 function. CONCLUSIONS: This suggests that in human, as in experimental models, severe prolonged hyperphosphatemia may be sufficient to produce bone differentiation proteins in vascular cells, and vascular calcification severe enough to require amputation. Genetic modifiers may contribute to the phenotypic variation within and between families.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationShah, A., Miller, C. J., Nast, C. C., Adams, M. D., Truitt, B., Tayek, J. A., … Iyengar, S. K. (2014). Severe vascular calcification and tumoral calcinosis in a family with hyperphosphatemia: a fibroblast growth factor 23 mutation identified by exome sequencing. Nephrology Dialysis Transplantation, 29(12), 2235–2243. http://doi.org/10.1093/ndt/gfu324en_US
dc.identifier.issn1460-2385en_US
dc.identifier.urihttps://hdl.handle.net/1805/11484
dc.language.isoen_USen_US
dc.publisherOxford University Pressen_US
dc.relation.isversionof10.1093/ndt/gfu324en_US
dc.relation.journalNephrology, Dialysis, Transplantation: Official Publication of the European Dialysis and Transplant Association - European Renal Associationen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectCalcinosisen_US
dc.subjectgeneticsen_US
dc.subjectDNAen_US
dc.subjectFibroblast Growth Factorsen_US
dc.subjectHyperostosis, Cortical, Congenitalen_US
dc.subjectHyperphosphatemiaen_US
dc.subjectMutationen_US
dc.subjectPhosphatesen_US
dc.subjectblooden_US
dc.subjectVascular Calcificationen_US
dc.titleSevere vascular calcification and tumoral calcinosis in a family with hyperphosphatemia: a fibroblast growth factor 23 mutation identified by exome sequencingen_US
dc.typeArticleen_US
ul.alternative.fulltexthttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240183/en_US
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