One of the major causes of congenital hypophosphatemic rickets is the X-linked hypophosphatemic rickets (XHR), due to a defect on PHEX gene. The XHR increases the renal elimination of phosphate, that condition leads a...One of the major causes of congenital hypophosphatemic rickets is the X-linked hypophosphatemic rickets (XHR), due to a defect on PHEX gene. The XHR increases the renal elimination of phosphate, that condition leads a defective mineralization of bones and also affects the growth in children. Clinical diagnosis should be suspected in children with signs of rickets and hypophosphatemia with normal calcium levels. We describe clinical characteristics and genetic results of four patients diagnosed and treated in our Nephrology Section. All patients have a “de novo” XHR as none familiars are affected. Early diagnosis should be suspected before the bone deformities have been submitted and the growth would have been impaired.展开更多
Hypophosphatemic vitamin D-resistant rickets or X-linked hypophosphatemia （XLH） is a rare hereditary metabolic disease manifesting marked hypophosphatemia, short stature and rickets. Its prevalence is approximately ...Hypophosphatemic vitamin D-resistant rickets or X-linked hypophosphatemia （XLH） is a rare hereditary metabolic disease manifesting marked hypophosphatemia, short stature and rickets. Its prevalence is approximately 1 in 20 000. Except early exfoliation of the teeth, there are a few oral findings of XLH described in China. Here we present two cases in one family.展开更多
A decade ago, only two hormones, parathyroid hormone and 1,25（OH）2D, were widely recognized to direct-ly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 （FGF23） in 2000 （1）, our ...A decade ago, only two hormones, parathyroid hormone and 1,25（OH）2D, were widely recognized to direct-ly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 （FGF23） in 2000 （1）, our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteo- blasts in the skeleton （2-3）, it modulates kidney handling of phosphate reabsorption and calcitriol produc-tion. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimentalto humans. In this review, we will discuss the vathovhvsiology of FGF23 and hvver-FGF23 related renal vhosvhate wasting disorders （4）.展开更多
Dentin matrix protein 1（DMP1） is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is cons...Dentin matrix protein 1（DMP1） is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is considered as an extracellular matrix protein that promotes hydroxyapatite formation and activates intracellular signaling pathway via interacting with avb3 integrin. Recent in vitro studies suggested that DMP1 might also act as a transcription factor. In this study, we examined whether full-length DMP1 could function as a transcription factor in the nucleus and regulate odontogenesis in vivo. We first demonstrated that a patient with the DMP1M1 V mutation, which presumably causes a loss of the secretory DMP1 but does not affect the nuclear translocation of DMP1, shows a typical rachitic tooth defect. Furthermore, we generated transgenic mice expressingNLSDMP1, in which the endoplasmic reticulum（ER） entry signal sequence of DMP1 was replaced by a nuclear localization signal（NLS） sequence, under the control of a 3.6 kb rat type I collagen promoter plus a 1.6 kb intron 1. We then crossbred theNLSDMP1 transgenic mice with Dmp1 null mice to express the NLSDMP1 in Dmp1-deficient genetic background. Although immunohistochemistry demonstrated thatNLSDMP1 was localized in the nuclei of the preodontoblasts and odontoblasts, the histological, morphological and biochemical analyses showed that it failed to rescue the dental and periodontal defects as well as the delayed tooth eruption in Dmp1 null mice. These data suggest that the full-length DMP1 plays no apparent role in the nucleus during odontogenesis.展开更多
X-连锁低血磷性佝偻病(X-linked hypophosphatemic rickets,XLH)是伴X染色体显性遗传的罕见病。其临床表型差异较大,即使是同一个家系,临床表现的轻重也有所差异。这可能与位于X染色体上与内肽酶同源的磷酸盐调节基因(phosphate-regulat...X-连锁低血磷性佝偻病(X-linked hypophosphatemic rickets,XLH)是伴X染色体显性遗传的罕见病。其临床表型差异较大,即使是同一个家系,临床表现的轻重也有所差异。这可能与位于X染色体上与内肽酶同源的磷酸盐调节基因(phosphate-regulating gene with homologies to endopeptidases on X chromosome,PHEX)突变有关。本文从PHEX基因的突变类型、突变位点以及突变剂量方面,对XLH基因型和临床表型的相关性予以综述,以期为XLH的基因研究与早期临床诊疗提供依据。展开更多
文摘One of the major causes of congenital hypophosphatemic rickets is the X-linked hypophosphatemic rickets (XHR), due to a defect on PHEX gene. The XHR increases the renal elimination of phosphate, that condition leads a defective mineralization of bones and also affects the growth in children. Clinical diagnosis should be suspected in children with signs of rickets and hypophosphatemia with normal calcium levels. We describe clinical characteristics and genetic results of four patients diagnosed and treated in our Nephrology Section. All patients have a “de novo” XHR as none familiars are affected. Early diagnosis should be suspected before the bone deformities have been submitted and the growth would have been impaired.
文摘Hypophosphatemic vitamin D-resistant rickets or X-linked hypophosphatemia （XLH） is a rare hereditary metabolic disease manifesting marked hypophosphatemia, short stature and rickets. Its prevalence is approximately 1 in 20 000. Except early exfoliation of the teeth, there are a few oral findings of XLH described in China. Here we present two cases in one family.
文摘患者,男,47岁,45年前无明显诱因出现双膝内翻畸形,双腿行走呈“O”型,而后畸形逐渐加重,双下肢酸痛,行走呈“剪刀”步态,需要拄拐。就诊前1年来,患者行走困难,并出现右踝关节疼痛,于2017年7月7日在临沂市人民医院骨科就诊。查体:“剪刀”步态,双膝呈内翻畸形,双大腿、小腿内旋畸形,左下肢长约710 mm.
基金supported by the National Natural Science Foundation of China (No.81070687 and 8117-0805)National Science and Technology Major Projects for"Major New Drugs Innovation and Development"(Grant No.2008ZX09312-016)Beijing Natural Science Foundation(No.7121012)
文摘A decade ago, only two hormones, parathyroid hormone and 1,25（OH）2D, were widely recognized to direct-ly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 （FGF23） in 2000 （1）, our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteo- blasts in the skeleton （2-3）, it modulates kidney handling of phosphate reabsorption and calcitriol produc-tion. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimentalto humans. In this review, we will discuss the vathovhvsiology of FGF23 and hvver-FGF23 related renal vhosvhate wasting disorders （4）.
基金supported by NIH grants DE018486 and R56 DE022789 to Jian-Quan Feng, DE023365 to Yong-Bo Lu and a scholarship from the Chinese State Scholarship Fund to Shu-Xian Lin (2010627108)
文摘Dentin matrix protein 1（DMP1） is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is considered as an extracellular matrix protein that promotes hydroxyapatite formation and activates intracellular signaling pathway via interacting with avb3 integrin. Recent in vitro studies suggested that DMP1 might also act as a transcription factor. In this study, we examined whether full-length DMP1 could function as a transcription factor in the nucleus and regulate odontogenesis in vivo. We first demonstrated that a patient with the DMP1M1 V mutation, which presumably causes a loss of the secretory DMP1 but does not affect the nuclear translocation of DMP1, shows a typical rachitic tooth defect. Furthermore, we generated transgenic mice expressingNLSDMP1, in which the endoplasmic reticulum（ER） entry signal sequence of DMP1 was replaced by a nuclear localization signal（NLS） sequence, under the control of a 3.6 kb rat type I collagen promoter plus a 1.6 kb intron 1. We then crossbred theNLSDMP1 transgenic mice with Dmp1 null mice to express the NLSDMP1 in Dmp1-deficient genetic background. Although immunohistochemistry demonstrated thatNLSDMP1 was localized in the nuclei of the preodontoblasts and odontoblasts, the histological, morphological and biochemical analyses showed that it failed to rescue the dental and periodontal defects as well as the delayed tooth eruption in Dmp1 null mice. These data suggest that the full-length DMP1 plays no apparent role in the nucleus during odontogenesis.
文摘X-连锁低血磷性佝偻病(X-linked hypophosphatemic rickets,XLH)是伴X染色体显性遗传的罕见病。其临床表型差异较大,即使是同一个家系,临床表现的轻重也有所差异。这可能与位于X染色体上与内肽酶同源的磷酸盐调节基因(phosphate-regulating gene with homologies to endopeptidases on X chromosome,PHEX)突变有关。本文从PHEX基因的突变类型、突变位点以及突变剂量方面,对XLH基因型和临床表型的相关性予以综述,以期为XLH的基因研究与早期临床诊疗提供依据。
