A deleterious mutation in SAMD9 causes normophosphatemic familial tumoral calcinosis

作者：Topaz Orit; Indelman Margarita; Chefetz Ilana; Geiger Dan; Metzker Aryeh; Altschuler Yoram; Choder Mordechai; Bercovich Dani; Uitto Jouni; Bergman Reuven; Richard Gabriele; Sprecher Eli^*

来源：American Journal of Human Genetics, 2006, 79(4): 759-764.

DOI：10.1086/508069

Familial tumoral calcinosis (FTC) is a rare autosomal recessive disorder characterized by the progressive deposition of calcified masses in cutaneous and subcutaneous tissues, which results in painful ulcerative lesions and severe skin and bone infections. Two major types of FTC have been recognized: hyperphosphatemic FTC (HFTC) and normophosphatemic FTC (NFTC). HFTC was recently shown to result from mutations in two different genes: GALNT3, which codes for a glycosyltransferase, and FGF23, which codes for a potent phosphaturic protein. To determine the molecular cause of NFTC, we performed homozygosity mapping in five affected families of Jewish Yemenite origin and mapped NFTC to 7q21-7q21.3. Mutation analysis revealed a homozygous mutation in the SAMD9 gene (K1495E), which was found to segregate with the disease in all families and to interfere with the protein expression. Our data suggest that SAMD9 is involved in the regulation of extraosseous calcification, a process of considerable importance in a wide range of diseases as common as atherosclerosis and autoimmune disorders.

• 出版日期2006-10