A novel homozygous missense mutation in FGF23 causes Familial Tumoral Calcinosis associated with disseminated visceral calcification
A novel homozygous missense mutation in FGF23 causes Familial Tumoral Calcinosis associated with disseminated visceral calcification
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DOI：
10.1007/s00439-005-0026-8
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发表时间：
2005-11-01
期刊：
影响因子：
5.3
通讯作者：
Schoenau, E
中科院分区：
文献类型：
--
作者：
Chefetz, I;Heller, R;Schoenau, E
高磷血症家族性肿瘤钙化病（HFTC, MIM211900）是一种罕见的常染色体隐性遗传病，其特征是皮肤和皮下组织中钙化肿块的进行性沉积，与循环中磷酸盐水平升高有关。该疾病最初被发现是由编码糖基转移酶的GALNT3突变引起的。然而，最近在两个家族中发现了编码一种强效磷酸蛋白的FGF23的S71G错义突变。在本报告中，我们描述了FGF23的第二种突变，其潜在的严重病例显示皮肤和许多皮外组织的钙化。发现该突变（M96T）影响了位于蛋白第96位的高度保守的蛋氨酸残基。这些观察结果说明了HFTC遗传和表型异质性的程度。
Hyperphosphatemic Familial Tumoral Calcinosis (HFTC; MIM211900) is a rare autosomal recessive disorder characterized by the progressive deposition of calcified masses in cutaneous and subcutaneous tissues, associated with elevated circulating levels of phosphate. The disease was initially found to result from mutations in GALNT3 encoding a glycosyltransferase. However, more recently, the S71G missense mutation in FGF23, encoding a potent phosphaturic protein, was identified in two families. In the present report, we describe a second mutation in FGF23 underlying a severe case displaying calcifications of cutaneous and numerous extracutaneous tissues. The mutation (M96T) was found to affect a highly conserved methionine residue at position 96 of the protein. These observations illustrate the extent of genetic and phenotypic heterogeneity in HFTC.