Hypophosphatemia and growth

Santos, Fernando; Fuente, Rocío Aller de la; Mejía, Natalia; Mantecón, Laura; Gil‐Peña, Helena; Ordoñez, Flor A.

doi:10.1007/s00467-012-2364-9

Cited by 58 publications

(51 citation statements)

References 70 publications

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“…X-linked hypophosphatemic rickets is the seminal example of excess FGF23 action. It can be diagnosed during the first year when suspected by family history and early onset of hypophosphatemia (452), but in the absence of family history it more often presents at 2 or 3 years of age with bowing of the long bones or growth failure, or at later ages with short stature (102,172,588). In four cases in which affected parents prompted an early diagnosis, serum phosphorus was low in all four between 2 and 6 wk of age, tubular reabsorption of phosphorus was low at 9 days of age in one but normal in the others until 6 mo, and radiographic findings of rickets did not develop until 3-6 mo (452).…”

Section: E Human Datamentioning

confidence: 99%

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

Kovacs

2014

Physiological Reviews

208

188

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Mineral and bone metabolism are regulated differently in utero compared with the adult. The fetal kidneys, intestines, and skeleton are not dominant sources of mineral supply for the fetus. Instead, the placenta meets the fetal need for mineral by actively transporting calcium, phosphorus, and magnesium from the maternal circulation. These minerals are maintained in the fetal circulation at higher concentrations than in the mother and normal adult, and such high levels appear necessary for the developing skeleton to accrete a normal amount of mineral by term. Parathyroid hormone (PTH) and calcitriol circulate at low concentrations in the fetal circulation. Fetal bone development and the regulation of serum minerals are critically dependent on PTH and PTH-related protein, but not vitamin D/calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, the serum calcium falls and phosphorus rises before gradually reaching adult values over the subsequent 24 -48 h. The intestines are the main source of mineral for the neonate, while the kidneys reabsorb mineral, and bone turnover contributes mineral to the circulation. This switch in the regulation of mineral homeostasis is triggered by loss of the placenta and a postnatal fall in serum calcium, and is followed in sequence by a rise in PTH and then an increase in calcitriol. Intestinal calcium absorption is initially a passive process facilitated by lactose, but later becomes active and calcitriol-dependent. However, calcitriol's role can be bypassed by increasing the calcium content of the diet, or by parenteral administration of calcium.

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Section: E Human Datamentioning

confidence: 99%

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

Kovacs

2014

Physiological Reviews

208

188

View full text Add to dashboard Cite

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“…Familial HR consists of a group of renal phosphate wasting disorders with hypophosphatemia and inappropriately low or normal serum 1,25-dihydroxyvitamin D (1,25(OH) 2 D) levels (Morey et al, 2011). Familial HR is characterized by marked clinical variability of growth retardation, childhood rickets, osteomalacia, and poor dental development (Dixon et al, 1998;Goji et al, 2006;Morey et al, 2011;Santos et al, 2013). In addition, extraskeletal bone formation, osteoarthritis, limitation of joint mobility, and occasionally spinal cord compression may occur (Dixon et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…It was reported that average incidence of HR is 3.9 per 100,000 in children between age 0 and 0.9 years, and a prevalence of 4.8 per 100,000 in those younger than 15 years (Beck-Nielsen et al, 2009). Six types of hereditary HR have been identified, including the common X-linked dominant HR (XLHR, MIM 307800), the occasional autosomal dominant HR (ADHR, MIM 193100), autosomal recessive HR (ARHR1, MIM 241520, and ARHR2, MIM 613312), the rare X-linked recessive HR (MIM 300554), and two peculiar rare forms of HR associated with hypercalciuria (HHRH, MIM 241530) and hyperparathyroidism (MIM 612089) (Morey et al, 2011;Baroncelli et al, 2012;Santos et al, 2013). HR may be caused by mutations of genes involved in the complex regulation of phosphate metabolism (Baroncelli et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing

Yuan

et al. 2014

Biological Chemistry

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Familial hypophosphatemic rickets (HR), the most common inherited form of rickets, is a group of inherited renal phosphate wasting disorders characterized by growth retardation, rickets with bone deformities, osteomalacia, poor dental development, and hypophosphatemia. The purpose of this study was to identify the genetic defect responsible for familial HR in a four-generation Chinese Han pedigree by exome sequencing and Sanger sequencing. Clinical features include skeletal deformities, teeth abnormalities, hearing impairments and variable serum phosphate level in patients of this family. A novel deletion mutation, c.1553delT (p.F518Sfs*4), was identified in the X-linked phosphate regulating endopeptidase homolog gene (PHEX). The mutation is predicted to result in prematurely truncated and loss-of-function PHEX protein. Our data suggest that exome sequencing is a powerful tool to discover mutation(s) in HR, a disorder with genetic and clinical heterogeneity. The findings may also provide new insights into the cause and diagnosis of HR, and have implications for genetic counseling and clinical management.

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“…The system of SSC-based gene therapy, in addition to the potential use in cases in which the father carries a homozygous genetic defect, could also be applied to treat the following genetic conditions: (1) male infertility induced by genetic defects, (2) father-carrying dominant disease alleles, and (3) sex chromosome-linked dominant genetic diseases [46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Correction of a genetic disease by CRISPR-Cas9-mediated gene editing in mouse spermatogonial stem cells

et al. 2014

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Spermatogonial stem cells (SSCs) can produce numerous male gametes after transplantation into recipient testes, presenting a valuable approach for gene therapy and continuous production of gene-modified animals. However, successful genetic manipulation of SSCs has been limited, partially due to complexity and low efficiency of currently available genetic editing techniques. Here, we show that efficient genetic modifications can be introduced into SSCs using the CRISPR-Cas9 system. We used the CRISPR-Cas9 system to mutate an EGFP transgene or the endogenous Crygc gene in SCCs. The mutated SSCs underwent spermatogenesis after transplantation into the seminiferous tubules of infertile mouse testes. Round spermatids were generated and, after injection into mature oocytes, supported the production of heterozygous offspring displaying the corresponding mutant phenotypes. Furthermore, a disease-causing mutation in Crygc (Crygc −/− ) that pre-existed in SSCs could be readily repaired by CRISPR-Cas9-induced nonhomologous end joining (NHEJ) or homology-directed repair (HDR), resulting in SSC lines carrying the corrected gene with no evidence of off-target modifications as shown by whole-genome sequencing. Fertilization using round spermatids generated from these lines gave rise to offspring with the corrected phenotype at an efficiency of 100%. Our results demonstrate efficient gene editing in mouse SSCs by the CRISPR-Cas9 system, and provide the proof of principle of curing a genetic disease via gene correction in SSCs. Keywords: CRISPR-Cas9; spermatogonial stem cell; gene therapy Cell Research (2015) IntroductionSpermatogonial stem cells (SSCs) can self-renew and undergo spermatogenesis, leading to the production of numerous spermatozoa, which transmit the genetic information to the next generation [1,2]. SSCs from different species can be maintained in vitro for long periods of time in medium supplemented with glial cell line-derived neurotrophic factor (GDNF) [3][4][5][6][7]. Meanwhile, after transplantation into the testes of an infertile male, cultured SSCs can re-establish spermatogenesis and restore fertility [1,8,9]. As genetic manipulation of SSCs and the subsequent transplantation allow one to select for desired genetic modifications, these techniques hold great promise in producing gene-modified animal models and particularly in treating genetic diseases with the potential of generating healthy progeny at 100% efficiency [1,10]. However, so far there have been very limited reports of using these techniques for efficient production of gene-modified animals [11,12], and their use in genetic disease correction has not yet been reported, partially due to complexity and low efficiency of currently available genetic editing techniques.Recently, the CRISPR-Cas9 system from bacteria has enabled rapid genome editing in different species at a very high efficiency and specificity [13][14][15][16][17]. CRIS-PR-Cas9-mediated genome editing requires only a short single-guide RNA (sgRNA) to guide site-specific DNA recogni...

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Hypophosphatemia and growth

Cited by 58 publications

References 70 publications

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing

Correction of a genetic disease by CRISPR-Cas9-mediated gene editing in mouse spermatogonial stem cells

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