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Abstract：
Human disorders of phosphate (Pi) handling and skeletal mineralization represent a group of rare bone diseases. One of these disease is tumoral calcinosis (TC). In this study, we present the case of a patient with TC with a new GALNT3 gene mutation. We also performed functional studies using an in vitro cellular model. Genomic DNA was extracted from peripheral blood collected from a teenage Caucasian girl affected by TC, and from her parents. A higher capability to form mineralization nodules in vitro was found in human preosteoblastic cells of mutant when compared to wild-type controls. We found a novel homozygous inactivating splice site mutation in intron I (c.516-2a>g). A higher capability to form mineralization nodules in vitro was found in the mutant cells in human preosteoblastic cells when compared to wild-type controls. Understanding the functional significance and molecular physiology of this novel mutation will help to define the role of FGF23 in the control of Pi homeostasis in normal and in pathological conditions.
摘要：
人类磷酸盐（Pi）处理和骨骼矿化疾病代表了一组罕见的骨骼疾病。这些疾病之一是肿瘤钙质沉着症(TC)。在这项研究中,我们介绍了一例TC患者的GALNT3基因突变新的病例.我们还使用体外细胞模型进行了功能研究。基因组DNA是从一名受TC影响的青少年高加索女孩的外周血中提取的，和她的父母。与野生型对照相比，在突变的人类前成骨细胞中发现了更高的体外形成矿化结节的能力。我们在内含子I中发现了一个新的纯合子失活剪接位点突变(c.516-2a>g)。与野生型对照相比，在人前成骨细胞的突变细胞中发现了更高的体外形成矿化结节的能力。了解这种新突变的功能意义和分子生理学将有助于确定FGF23在正常和病理条件下控制Pi稳态中的作用。
