A Deleterious Mutation in SAMD9 Causes Normophosphatemic Familial Tumoral Calcinosis
| Autor: | Mordechai Choder, Aryeh Metzker, Dan Geiger, Gabriele Richard, Eli Sprecher, Reuven Bergman, Ilana Chefetz, Orit Topaz, Yoram Altschuler, Margarita Indelman, Dani Bercovich, Jouni Uitto |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Pathology Skin Neoplasms medicine.disease_cause 0302 clinical medicine Genetics(clinical) Genetics (clinical) 0303 health sciences Mutation Intracellular Signaling Peptides and Proteins Calcinosis Extraosseous Calcification Disease gene identification Gingivitis 3. Good health Pedigree 030220 oncology & carcinogenesis Tumoral calcinosis Female medicine.symptom medicine.medical_specialty Green Fluorescent Proteins Biology Transfection Skin Diseases Cell Line 03 medical and health sciences Internal medicine Report Skin Ulcer medicine Genetics Humans Family Amino Acid Sequence 030304 developmental biology Haplotype Infant Proteins Skin ulcer medicine.disease Conjunctivitis Fibroblast Growth Factor-23 Endocrinology Amino Acid Substitution Haplotypes Lod Score Sequence Alignment Calcification |
| Zdroj: | The American Journal of Human Genetics. 79(4):759-764 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/508069 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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