Genetic analysis of three families with X-linked dominant hypophosphatemic rickets

Lin, Xin-Fu; Zhu, Yao‐Bin; Luo, Jie‐Wei; Huang, Jianbin

doi:10.1515/jpem-2017-0451

Cited by 8 publications

(11 citation statements)

References 36 publications

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“…FGF23 has been shown to inhibit PTH synthesis and secretion directly through the MAPK pathway both in animals and in vitro . However, in particular chronic kidney disease (CKD) is widely known to be associated with elevated serum PTH . One aspect explaining this discrepancy could be that FGF23 can regulate PTH predominantly under physiological conditions and less in disease for hitherto unknown reasons.…”

Section: Fgf23: a Phosphaturic Hormonementioning

confidence: 99%

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Regulation of fibroblast growth factor 23 (FGF23) in health and disease

et al. 2019

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Fibroblast growth factor 23 (FGF23) is mainly produced in the bone and, upon secretion, forms a complex with a FGF receptor and coreceptor αKlotho. FGF23 can exert several endocrine functions, such as inhibiting renal phosphate reabsorption and 1,25‐dihydroxyvitamin D3 production. Moreover, it has paracrine activities on several cell types, including neutrophils and hepatocytes. Klotho and Fgf23 deficiencies result in pathologies otherwise encountered in age‐associated diseases, mainly as a result of hyperphosphataemia‐dependent calcification. FGF23 levels are also perturbed in the plasma of patients with several disorders, including kidney or cardiovascular diseases. Here, we review mechanisms controlling FGF23 production and discuss how FGF23 regulation is perturbed in disease.

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Section: Fgf23: a Phosphaturic Hormonementioning

confidence: 99%

“…X‐linked hypophosphataemia is linked to a loss‐of‐function mutation of the membrane‐bound metalloendopeptidase PHEX (phosphate‐regulating gene with homologies to endopeptidases on the X chromosome) . Although it is a peptidase expressed in bone, PHEX does not cleave FGF23 .…”

Section: Fgf23 Regulation: Insights From Rare Disorders and Renal Dismentioning

confidence: 99%

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

et al. 2019

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“…Short stature and rachitic osseous lesions are characteristic features of XLH, although the severity of these manifestations is highly variable among patients [ 42 ]. Recently, a new nonsense mutation (p.E145*) in exon 4 of PHEX has been predicted to be responsible for XLH [ 83 ]. Animal models of XLH have demonstrated a defect in PT phosphate reabsorption and decreased expression of NaPi-IIa and NaPi-IIc [ 144 – 146 ].…”

Section: Disorders Pi Balancementioning

confidence: 99%

Physiological regulation of phosphate by vitamin D, parathyroid hormone (PTH) and phosphate (Pi)

Jacquillet

Unwin

2018

Pflugers Arch - Eur J Physiol

101

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Inorganic phosphate (Pi) is an abundant element in the body and is essential for a wide variety of key biological processes. It plays an essential role in cellular energy metabolism and cell signalling, e.g. adenosine and guanosine triphosphates (ATP, GTP), and in the composition of phospholipid membranes and bone, and is an integral part of DNA and RNA. It is an important buffer in blood and urine and contributes to normal acid-base balance. Given its widespread role in almost every molecular and cellular function, changes in serum Pi levels and balance can have important and untoward effects. Pi homoeostasis is maintained by a counterbalance between dietary Pi absorption by the gut, mobilisation from bone and renal excretion. Approximately 85% of total body Pi is present in bone and only 1% is present as free Pi in extracellular fluids. In humans, extracellular concentrations of inorganic Pi vary between 0.8 and 1.2 mM, and in plasma or serum Pi exists in both its monovalent and divalent forms (H2PO4− and HPO42−). In the intestine, approximately 30% of Pi absorption is vitamin D regulated and dependent. To help maintain Pi balance, reabsorption of filtered Pi along the renal proximal tubule (PT) is via the NaPi-IIa and NaPi-IIc Na+-coupled Pi cotransporters, with a smaller contribution from the PiT-2 transporters. Endocrine factors, including, vitamin D and parathyroid hormone (PTH), as well as newer factors such as fibroblast growth factor (FGF)-23 and its coreceptor α-klotho, are intimately involved in the control of Pi homeostasis. A tight regulation of Pi is critical, since hyperphosphataemia is associated with increased cardiovascular morbidity in chronic kidney disease (CKD) and hypophosphataemia with rickets and growth retardation. This short review considers the control of Pi balance by vitamin D, PTH and Pi itself, with an emphasis on the insights gained from human genetic disorders and genetically modified mouse models.

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“…To date, research studies in XLH have focussed largely on increasing knowledge around the disease mechanism and the understanding of its clinical manifestations [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. There have been few studies exploring the patient perspective of living with symptoms of XLH and impact of current treatment [21].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Burden of X-Linked Hypophosphataemia: An Opportunistic Qualitative Study of Patient Statements Generated During a Technology Appraisal

et al. 2019

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Introduction: Capturing the patient experience of living with a rare disease such as X-linked hypophosphataemia (XLH) is critical for a holistic understanding of the burden of a disease. The complexity of the disease coupled with the limited population makes elicitation of the patient burden methodologically challenging. This study used qualitative information direct from patient and caregiver statements to assess the burden of XLH. Methods: A thematic analysis was conducted on statements received during a National Institute for Health and Care Excellence (NICE) online public open consultation from 15 June to 6 July 2018. Researchers and clinical experts generated themes and codes based on expected aspects of XLH burden. Statements were independently coded by two reviewers, adding additional codes as required, and analysed by frequency and co-reporting across age groups. Results: The majority of responses were submitted from UK-based patients with some from the USA and Australia, and the statements related to children, adolescents and adults. The findings suggest that the greatest burden experienced by children is associated with conventional therapy, co-reported with dosing regimen, adherence, distress and pain. During adolescence, the burden becomes increasingly complex and multi-factorial, with an increasing psychological burden. In adults, conventional therapy co-reported with bone deformity and Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.11336099.

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Genetic analysis of three families with X-linked dominant hypophosphatemic rickets

Cited by 8 publications

References 36 publications

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

Physiological regulation of phosphate by vitamin D, parathyroid hormone (PTH) and phosphate (Pi)

Exploring the Burden of X-Linked Hypophosphataemia: An Opportunistic Qualitative Study of Patient Statements Generated During a Technology Appraisal

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