| H01193 | |
| H number | H01193 |
| Name | Familial tumoral calcinosis |
| Description | Familial tumoral calcinosis (FTC) refers to a group of disorders inherited in an autosomal recessive fashion, distinguished by the development of ectopic and vascular calcified masses that occur in settings of hyperphosphatemia (hFTC) and normophosphatemia (nFTC). hFTC is characterized by increased re-absorption of phosphate through the renal proximal tubule, resulting in elevated phosphate concentration and deposition of calcified deposits in cutaneous and subcutaneous tissues, occasionally, in visceral organs. hFTC has been shown to result from mutations in three genes: fibroblast growth factor-23 (FGF23), KL encoding Klotho, and GALNT3, which encodes a glycosyltransferase responsible for FGF23 O-glycosylation; defective function of any one of these three proteins results in hyperphosphatemia and ectopic calcification. nFTC is characterized by absence of metabolic abnormalities. nFTC has been found to be associated with absence of functional SAMD9, a putative tumor suppressor and anti-inflammatory protein. |
| Category | Inherited metabolic disorder |
| Network | - |
| Gene | (HFTC1) GALNT3 [HSA:2591] [KO:K00710] (HFTC2) FGF23 [HSA:8074] [KO:K22428] (HFTC3) KL [HSA:9365] [KO:K14756] (NFTC) SAMD9 [HSA:54809] [KO:K23949] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 5C54.1 ICD-10: M11.2 MeSH: C566870 C566473 OMIM: 211900 617993 617994 610455 |
| Reference | PMID:19865099 AUTHORS Sprecher E TITLE Familial tumoral calcinosis: from characterization of a rare phenotype to the pathogenesis of ectopic calcification. JOURNAL J Invest Dermatol 130:652-60 (2010) DOI:10.1038/jid.2009.337 PMID:22142751 AUTHORS Farrow EG, Imel EA, White KE TITLE Miscellaneous non-inflammatory musculoskeletal conditions. Hyperphosphatemic familial tumoral calcinosis (FGF23, GALNT3 and alphaKlotho). JOURNAL Best Pract Res Clin Rheumatol 25:735-47 (2011) DOI:10.1016/j.berh.2011.10.020 PMID:19013236 AUTHORS Chefetz I, Sprecher E TITLE Familial tumoral calcinosis and the role of O-glycosylation in the maintenance of phosphate homeostasis. JOURNAL Biochim Biophys Acta 1792:847-52 (2009) DOI:10.1016/j.bbadis.2008.10.008 PMID:15133511 (GALNT3) AUTHORS Topaz O, Shurman DL, Bergman R, Indelman M, Ratajczak P, Mizrachi M, Khamaysi Z, Behar D, Petronius D, Friedman V, Zelikovic I, Raimer S, Metzker A, Richard G, Sprecher E TITLE Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. JOURNAL Nat Genet 36:579-81 (2004) DOI:10.1038/ng1358 PMID:15590700 (FGF23) AUTHORS Benet-Pages A, Orlik P, Strom TM, Lorenz-Depiereux B TITLE An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia. JOURNAL Hum Mol Genet 14:385-90 (2005) DOI:10.1093/hmg/ddi034 PMID:17710231 (KL) AUTHORS Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH, Goetz R, Mohammadi M, White KE, Econs MJ TITLE A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. JOURNAL J Clin Invest 117:2684-91 (2007) DOI:10.1172/JCI31330 PMID:16960814 (SAMD9) AUTHORS Topaz O, Indelman M, Chefetz I, Geiger D, Metzker A, Altschuler Y, Choder M, Bercovich D, Uitto J, Bergman R, Richard G, Sprecher E TITLE A deleterious mutation in SAMD9 causes normophosphatemic familial tumoral calcinosis. JOURNAL Am J Hum Genet 79:759-64 (2006) DOI:10.1086/508069 |