A Novel Recessive Mutation of Fibroblast Growth Factor-23 in Tumoral Calcinosis

Masi, L.; Gozzini, A.; Franchi, A.; Campanacci, D.; Amedei, A.; Faichetti, A.; Franceschelli, F.; Marcucci, G.; Tanini, A.; Capanna, R.; Brandi, M. L.
May 2009
Journal of Bone & Joint Surgery, American Volume;May2009, Vol. 91-A Issue 5, p1190
Academic Journal
Background: Tumoral calcinosis is a rare disease characterized by hyperphosphatemia due to hypophosphaturia and by ectopic calcifications. Phosphatonins are important hormones that regulate phosphorus homeostasis. Tumoral calcinosis is a rare congenital disorder in which the differential diagnosis from other syndromes associated with extraskeletal calcifications may be difficult. Mutations in the UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-3 (GALNT3) and fibroblast growth factor-23 (FGF23) genes have been described. Mutational analysis is important for the early recognition of the disorder, for prevention of its complications, and for family screening strategies. We examined two unrelated white patients affected by tumoral calcinosis. Methods: The first patient was a woman with a history of an ectopic calcification in the left shoulder. The second patient was a man with a history of an ectopic calcification in the right buttock. Routine biochemistry and FGF-23 assays were performed on serum samples. Genomic DNA was extracted from peripheral blood. The FGF23 and GALNT3 genes were analyzed by direct sequencing. Results: A new homozygous H41Q codon 41, C →A transversion at position 123 (c.123C>A) in exon 1 of the FGF23 gene was evidenced in both patients. No mutation of the GALNT3 gene was detected in these patients. As determined by an ELISA assay, intact FGF-23 circulating protein was low in both patients. Conclusions: This is the fourth mutation of the FGF23 gene described in subjects with tumoral calcinosis. Clinical Relevance: The biochemical and clinical profile of the two unrelated patients bearing the mutation reinforces the relevant role of FGF-23 in bone metabolism and in the pathogenesis of tumoral calcinosis.


Related Articles

  • In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11. Varga, Rita-Eva; Khundadze, Mukhran; Damme, Markus; Nietzsche, Sandor; Hoffmann, Birgit; Stauber, Tobias; Koch, Nicole; Hennings, J. Christopher; Franzka, Patricia; Huebner, Antje K.; Kessels, Michael M.; Biskup, Christoph; Jentsch, Thomas J.; Qualmann, Britta; Braulke, Thomas; Kurth, Ingo; Beetz, Christian; Hübner, Christian A. // PLoS Genetics;8/18/2015, Vol. 11 Issue 8, p1 

    Hereditary spastic paraplegia (HSP) is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study...

  • EGFR mutation detection by microfluidic technology: a validation study. Malapelle, Umberto; Russo, Stefania; Pepe, Francesco; Sgariglia, Roberta; De Luca, Caterina; Bellevicine, Claudio; Pallante, Pierlorenzo; Troncone, Giancarlo // Journal of Clinical Pathology;Nov2013, Vol. 66 Issue 11, p982 

    Advanced non-small cell lung cancer samples are tested for epidermal growth factor receptor (EGFR) gene mutations. Their detection by direct sequencing is timeconsuming. Conversely, the length analysis of fluorescently labelled PCR products is easier. To avoid labelled primers and the automated...

  • Glioblastoma Genetics.  // BioWorld Today;12/27/2010, Vol. 21 Issue 248, Special section p2 

    The article offers information on a study which showed that he gene for NFkappaB inhibitor alpha (NFKBIA) is frequently deleted in glioblastoma subtypes that do not exhibit activating epidermal growth factor receptor (EGFR) mutations.

  • Study of Possible Genetic Factors Determining the Clinical Picture of Thalassemia Intermedia. Kaddah, N.; Rizk, S.; Kaddah, A. M.; Salama, K.; Lotfy, H. // Journal of Medical Sciences;2009, Vol. 9 Issue 3, p151 

    The aim of this study was to evaluate some of the genetic factors involved in ameliorating the severity of β thalassemia among a group of Egyptian children with thalassemia intermedia. The study included 22 patients who were diagnosed on clinical basis as β thalassemia intermedia. Their...

  • Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.  // BMC Medical Genetics;2011, Vol. 12 Issue 1, p106 

    The article presents a research on defects in Neurexin 1 (NRXN1) and contactin associated protein 2 (CNTNAP2) in patients with intellectual disability. In this study the patients with intellectual disability and Pitt-Hopkins syndrome were genetically screened for mutations in NRXN1 and CNTNAP2...

  • Pathogenetics. An introductory review. Zaghloul Salem, Mohammad Saad // Egyptian Journal of Medical Human Genetics;Jan2016, Vol. 17 Issue 1, p1 

    Pathogenetics refers to studying the different aspects of initiation/development/progres sion and pathogenesis of genetic defects. It comprises the study of mutagens or factors capable of affecting the structural integrity of the genetic material leading to mutational changes that, in the...

  • Two functionally distinct domains generated by in vivo cleavage of Nup145p: a novel biogenesis pathway for nucleoporins. Teixeira, Maria Teresa; Siniossoglou, Symeon; Podtelejnikov, Sasha; Benichou, Jean Claude; Mann, Mattias; Dujon, Bernard; Hurt, Ed; Fabre, Emmanuelle // EMBO Journal;8/15/97, Vol. 16 Issue 16, p5086 

    Nup145p is an essential yeast nucleoporin involved in nuclear export of polyadenylated RNAs. We demonstrate here that Nup145p is cleaved in vivo to yield two functionally distinct domains: a carboxy�terminal domain (C-Nup145p) which is located at the nuclear pore complex (NPC) and assembles...

  • Heterozygous P250L mutation of fibroblast growth factor receptor 3 in a case of isolated craniosynostosis. Schindler, S.; Friedrich, M.; Wagener, H.; Lorenz, B.; Preising, M.N. // Journal of Medical Genetics;Oct2002, Vol. 39 Issue 10, p764 

    Studies the heterozygous P250L mutation of fibroblast growth factor receptor 3 in a case of isolated craniosynostosis. Key issues of interest; Analysis of pertinent topics and relevant issues; Implications on medical genetics.

  • Optimal front line treatment for European patients harboring EGFR mutations: Do longitude and race make a difference? Landi, Lorenza; Cappuzzo, Federico // Journal of Thoracic Disease;Apr2012, Vol. 4 Issue 2, p226 

    The article discusses the optimal front line treatment for European patients harboring Epidermal Growth Factor Receptor (EGFR) mutations for patients with non-small-cell-lung cancer (NSCLC). The impact of both longitude and race on EGFR mutations, if any, is described. All available data...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics