A PHEX Gene Mutation Is Responsible for Adult-Onset Vitamin D-Resistant Hypophosphatemic Osteomalacia: Evidence That the Disorder Is Not a Distinct Entity from X-Linked Hypophosphatemic Rickets1

Econs, Michael J.; Friedman, Nancy; Rowe, Peter; Speer, Marcy C.; Francis, Fiona; Strom, Tim M.; Oudet, C.; Smith, John A.; Ninomiya, James T.; Lee, Benjamin E.; Bergen, Heather L.

doi:10.1210/jcem.83.10.5167

Cited by 16 publications

(4 citation statements)

References 10 publications

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“…53 Some human phosphate metabolism diseases can cause an altered level of FGF23. For instance, X-linked hypophosphatemia is caused by PHEX gene mutation, 54 however, the mutation in Dmp1 has been shown to be responsible for autosomal recessive hypophosphatemic rickets. Unexpectedly, in addition to phosphate metabolism, FGF23-deficient mice are characterized with hypoglycemia and increased insulin sensitivity.…”

Section: Bone-derived Factors and Their Actions On Musclementioning

confidence: 99%

Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis

Zhang

Wang

et al. 2019

J of Cellular Biochemistry

118

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The nature of muscle‐bone crosstalk has been historically considered to be only mechanical, where the muscle is the load applier while bone provides the attachment sites. However, this dogma has been challenged with the emerging notion that bone and muscle act as secretory endocrine organs affect the function of each other. Biochemical crosstalk occurs through myokines such as myostatin, irisin, interleukin (IL)‐6, IL‐7, IL‐15, insulin‐like growth factor‐1, fibroblast growth factor (FGF)‐2, and β‐aminoisobutyric acid and through bone‐derived factors including FGF23, prostaglandin E2, transforming growth factor β, osteocalcin, and sclerostin. Aside from the biochemical and mechanical interaction, additional factors including aging, circadian rhythm, nervous system network, nutrition intake, and exosomes also have effects on bone‐muscle crosstalk. Here, we summarize the current research progress in the area, which may be conductive to identify potential novel therapies for the osteoporosis and sarcopenia, especially when they develop in parallel.

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Section: Bone-derived Factors and Their Actions On Musclementioning

confidence: 99%

Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis

Zhang

Wang

et al. 2019

J of Cellular Biochemistry

118

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“…Our study is the first to evaluate the correlation between interpatellar or intercondylar distance and genotype; however, no significant correlation was identified. In fact, a huge phenotype variation between individuals with the same genotype was described, particularly regarding the skeletal phenotype ( 7 , 31 ).…”

Section: Discussionmentioning

confidence: 99%

A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype

Borghi,

Silva,

Bispo

et al. 2023

Front. Pediatr.

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AimX-linked hypophosphatemia (XLH) is the most common inherited form of rickets, and it is caused by pathogenic inactivating variants of the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. The main purpose of this study is to identify the presence of a genotype–phenotype correlation in a cohort of XLH patients.MethodsThis is a retrospective study including patients diagnosed with hypophosphatemic rickets, confirmed by clinical, radiological, and laboratory findings. Medical records were reviewed for phenotypic analyses. Genomic DNA was extracted from the peripheral blood lymphocytes, and PHEX sequencing was performed by exomic NGS sequencing. The Wilcoxon rank-sum test and the two-tailed Fisher's exact test were employed for the statistical analyses of this study.ResultsA total of 41 patients were included in this study, and 63.41% (26/41) of the patients were female. The mutation analyses identified 29.27% missense variants and 29.72% nonsense variants, most of them were considered deleterious (66.41%). Six novel deleterious variants in the PHEX gene were detected in seven patients. The median concentrations of pretreatment serum calcium, phosphorus, and parathyroid hormone (PTH) were not significantly different among patients with different genotypes. An orthopedic surgery due to bone deformity was required in 57.69%.ConclusionsOur analysis did not identify any specific genotype as a predictor. No significant genotype–phenotype correlation was found, suggesting that the recognition of subjacent pathogenic mutation in the PHEX gene may have limited prognostic value. Despite this finding, genetic testing may be useful for identifying affected individuals early and providing appropriate treatment.

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“…Fibroblast growth factor 23 (FGF-23) is the first hormonelike osteokine found to be secreted by bone cells (Liu et al, 2006). FGF23 gene mutation is the cause of autosomal dominant hypophosphatemic rickets (ADHRs) (Econs et al, 1998). FGF23 and parathyroid hormone (PTH) can jointly regulate phosphate metabolism (Quarles, 2012).…”

Section: Fgf-23 and Its Effect On Musclesmentioning

confidence: 99%

The Role of Osteokines in Sarcopenia: Therapeutic Directions and Application Prospects

Xiao

Xie

et al. 2021

Front. Cell Dev. Biol.

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Sarcopenia is an age-related disease in which muscle mass, strength and function may decline with age or can be secondary to cachexia or malnutrition and can lead to weakness, falls and even death. With the increase in life expectancy, sarcopenia has become a major threat to the health of the elderly. Currently, our understanding of bone-muscle interactions is not limited to their mechanical coupling. Bone and muscle have been identified as secretory endocrine organs, and their interaction may affect the function of each. Both muscle-derived factors and osteokines can play a role in regulating muscle and bone metabolism via autocrine, paracrine and endocrine mechanisms. Herein, we comprehensively summarize the latest research progress on the effects of the osteokines FGF-23, IGF-1, RANKL and osteocalcin on muscle to explore whether these cytokines can be utilized to treat and prevent sarcopenia.

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A PHEX Gene Mutation Is Responsible for Adult-Onset Vitamin D-Resistant Hypophosphatemic Osteomalacia: Evidence That the Disorder Is Not a Distinct Entity from X-Linked Hypophosphatemic Rickets1

Cited by 16 publications

References 10 publications

Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis

Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis

A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype

The Role of Osteokines in Sarcopenia: Therapeutic Directions and Application Prospects

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