1. ¹Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
2. ²Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel

Correspondence: Professor Eli Sprecher, Department of Dermatology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel. E-mail: elisp@tasmc.health.gov.il

Received 17 July 2009; Revised 18 August 2009; Accepted 25 August 2009; Published online 29 October 2009.

Abstract

Familial tumoral calcinosis (FTC) refers to a heterogeneous group of inherited disorders characterized by the occurrence of cutaneous and subcutaneous calcified masses. Two major forms of the disease are now recognized. Hyperphosphatemic FTC has been shown to result from mutations in three genes: fibroblast growth factor-23 (FGF23), coding for a potent phosphaturic protein, KL encoding Klotho, which serves as a co-receptor for FGF23, 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. The second form of the disease is characterized by absence of metabolic abnormalities, and is, therefore, termed normophosphatemic FTC. This variant was found to be associated with absence of functional SAMD9, a putative tumor suppressor and anti-inflammatory protein. The data gathered through the study of these rare disorders have recently led to the discovery of novel aspects of the pathogenesis of common disorders in humans, underscoring the potential concealed within the study of rare diseases.