Clinical variability of familial tumoral calcinosis caused by novel GALNT3mutationsShoji Ichikawa and Geneviève Baujat contributed equally to this work.Competing Interest: None to declare.How to cite this article: Ichikawa S, Baujat G, Seyahi A, Garoufali AG, Imel EA, Padgett LR, Austin AM, Sorenson AH, Pejin Z, Topouchian V, Quartier P, CormierDaire V, Dechaux M, Malandrinou FC, Singhellakis PN, Le Merrer M, Econs MJ. 2010. Clinical variability of familial tumoral calcinosis caused by novel GALNT3mutations. Am J Med Genet Part A 152A:896–903.

Autor: Ichikawa, Shoji, Baujat, Geneviève, Seyahi, Aksel, Garoufali, Anastasia G., Imel, Erik A., Padgett, Leah R., Austin, Anthony M., Sorenson, Andrea H., Pejin, Zagorka, Topouchian, Vicken, Quartier, Pierre, CormierDaire, Valerie, Dechaux, Michele, Malandrinou, Fotini Ch., Singhellakis, Panagiotis N., Le Merrer, Martine, Econs, Michael J.
Zdroj: American Journal of Medical Genetics. Part A; April 2010, Vol. 152 Issue: 4 p896-903, 8p
Abstrakt: The GALNT3gene encodes GalNAcT3, which prevents degradation of the phosphaturic hormone, fibroblast growth factor 23 FGF23. Biallelic mutations in either GALNT3or FGF23result in hyperphosphatemic familial tumoral calcinosis or its variant, hyperostosis–hyperphosphatemia syndrome. Tumoral calcinosis is characterized by the presence of ectopic calcifications around major joints, whereas hyperostosis–hyperphosphatemia syndrome is characterized by recurrent long bone lesions with hyperostosis. Here we investigated four patients with hyperphosphatemia and clinical manifestations including tumoral calcinosis andor hyperostosis–hyperphosphatemia syndrome to determine underlying genetic cause and delineate phenotypic heterogeneity of these disorders. Mutational analysis of FGF23and GALNT3in these patients revealed novel homozygous mutations in GALNT3. Although the presence of massive calcifications, cortical hyperostosis, or dental anomalies was not shared by all patients, all had persistent hyperphosphatemia. Three of the patients also had inappropriately normal 1,25dihyroxyvitamin D 1,25OH2D and confirmed low circulating intact FGF23 concentrations. The four novel GALNT3mutations invariably resulted in hyperphosphatemia as a result of low intact FGF23, but other clinical manifestations were variable. Therefore, tumoral calcinosis and hyperostosis–hyperphosphatemia syndrome represent a continuous spectrum of the same disease caused by increased phosphate levels, rather than two distinct disorders. © 2010 WileyLiss, Inc.
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