The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Matthew Garabedian - One of the best experts on this subject based on the ideXlab platform.
-
phex analysis in 118 pedigrees reveals new genetic clues in Hypophosphatemic Rickets
Human Genetics, 2009Co-Authors: Celine Gaucher, Odile Walrantdebray, Thyminh Nguyen, Laure Esterle, Matthew Garabedian, Frederic JehanAbstract:Familial Hypophosphatemic Rickets is a rare disease, which is mostly transmitted as an X-linked dominant trait, and mutations on the phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) gene are responsible for the disease in most Familial cases. In this study we analyzed PHEX in a large cohort of 118 pedigrees representing 56 Familial cases and 62 sporadic cases. The high-resolution melting curves technique was tested as a screening method, along with classical sequencing. PHEX mutations have been found in 87% of Familial cases but also in 72% of sporadic cases. Missense mutations were found in 16 probands, two of which being associated with other PHEX mutations resulting into truncated proteins. By plotting missense mutations described so far on a 3D model of PHEX we observed that these mutations focus on two regions located in the inner part of the PHEX protein. Family members of 13 sporadic cases were analyzed and a PHEX mutation was detected in one of the apparently healthy mother. These results highlight the major role of PHEX in X-linked dominant Hypophosphatemic Rickets, and give new clues regarding the genetic analysis of the disease. A screening of the different family members should be mandatory when a PHEX mutation is assessed in a sporadic case and the search for another PHEX mutation should be systematically proceed when facing a missense mutation.
-
Dentin Noncollagenous Matrix Proteins in Familial Hypophosphatemic Rickets
Cells tissues organs, 2008Co-Authors: Celine Gaucher, Frederic Jehan, D Septier, Matthew Garabedian, Tchilalo Boukpessi, Peter S.n. Rowe, Michel E. Goldberg, Catherine Chaussain-millerAbstract:Familial Hypophosphatemic Rickets is transmitted in most cases as an X-linked dominant trait and results from the mutation of the PHEX gene predominantly expressed in osteoblast and odontoblast. Patients with Rickets have been reported to display important dentin defects. Our purpose was to explore the structure, composition and distribution of noncollagenous proteins (NCPs) of Hypophosphatemic dentin. We collected teeth from 10 Hypophosphatemic patients whose mineralization occurred either in a Hypophosphatemic environment or in a corrected phosphate and vitamin environment. Teeth were examined by scanning electron microscopy, immunohistochemistry and Western blot analysis. An abnormal distribution (accumulation in interglobular spaces) and cleavage of the NCPs and particularly of matrix extracellular phosphoglycoprotein were observed in deciduous dentin. In contrast, it was close to normal in permanent dentin mineralized under corrected conditions. In conclusion, dentin mineralization in a corrected phosphate and vitamin D environment compensates the adverse effect of PHEX mutation.
-
dentin structure in Familial Hypophosphatemic Rickets benefits of vitamin d and phosphate treatment
Oral Diseases, 2007Co-Authors: C Chaussainmiller, Charlotte Sinding, D Septier, Maryse Wolikow, Michel Goldberg, Matthew GarabedianAbstract:Objective: To evaluate the outcome of 1-(OH) vitamin D and oral phosphate treatment on dentin structure in patients with Familial Hypophosphatemic Rickets, and expression of SIBLINGs (a family of non-collagenous proteins involved in dentinogenesis) and osteocalcin. Patients and methods: Seven patients with Familial Hypophosphatemic Rickets (age 3–16 years) were studied before or during treatment. Deciduous and permanent teeth were prepared for scanning electron microscopy (SEM) analysis and immunohistochemistry. Results: Untreated or inadequately treated patients had necrotic teeth with impaired dentin mineralization including unmerged calcospherites and accumulation of non-collagenous proteins in wide interglobular spaces. Most of the primary incisors analyzed displayed fissures linking enamel subsurface to pulp horn. These elements may explain the bacterial penetration and dental abscesses despite the absence of carious lesions. Well-treated patients had healthy teeth with good dentin mineralization and little evidence of calcospherites. Conclusion: Treatment of Hypophosphatemic children with 1-(OH) vitamin D and oral phosphate insures good dentin development and mineralization, and prevents clinical anomalies such as the dental necrosis classically associated with the disease. Starting treatment during early childhood and good adherence to the therapy are mandatory to observe these beneficial effects.
-
Dentin Alteration of Deciduous Teeth in Human Hypophosphatemic Rickets
Calcified Tissue International, 2006Co-Authors: Tchilalo Boukpessi, D Septier, Matthew Garabedian, S. Bagga, M. Goldberg, Catherine Chaussain-millerAbstract:Familial Hypophosphatemic Rickets is in most cases transmitted as an X-linked dominant trait and results from mutation of the PHEX gene, predominantly expressed in osteoblast and odontoblast. Patients have been reported to display important dentin defects, and therefore, we explored the dentin structure, composition, and distribution of extracellular matrix (ECM) molecules in Hypophosphatemic human deciduous teeth. Compared to age-matched controls, the dentin from Hypophosphatemic patients exhibited major differences: presence of large interglobular spaces resulting from the lack of fusion of calcospherites in the circumpulpal dentin; defective mineralization in the interglobular spaces contrasting with normal Ca-P levels in the calcospherites on X-ray microanalysis; abnormal presence of low-molecular weight protein complexes recognized on Western blots by antibodies against matrix extracellular phosphoglycoprotein (MEPE), dentin sialoprotein, osteopontin, and reduced osteocalcin (OC) level; and accumulation in the interglobular spaces of immunolabeling with antibodies against DSP, dentin matrix protein, bone sialoprotein, MEPE and OC, while chondroitin/dermatan sulfate glycosaminoglycans were exclusively located inside calcospherites. Alterations of the post-translational processing or partial degradation of some ECM appear as key factors in the formation of the defective Hypophosphatemic dentin.
Uri Alon - One of the best experts on this subject based on the ideXlab platform.
-
calcimimetics as an adjuvant treatment for Familial Hypophosphatemic Rickets
Clinical Journal of The American Society of Nephrology, 2008Co-Authors: Uri Alon, Wayne V. Moore, Rachel Levyolomucki, Jason R Stubbs, Darryl L QuarlesAbstract:Background and Objectives: The treatment for X-linked hypophosphatemia (XLH) with phosphate and calcitriol can be complicated by secondary hyperparathyroidism and nephrocalcinosis. Furthermore, vitamin D and phosphate stimulate FGF23 production, the pathogenic factor causing XLH. We investigated in XLH patients: 1) whether treatment with the calcimimetic agent, cinacalcet, will block the rise in parathyroid hormone (PTH) caused by phosphate administration; and 2) whether treatment with oral phosphate and calcitriol increases FGF23 levels. Design, Setting, Participants, and Measurements: Eight subjects with XLH were given a single oral dose of phosphate, followed the next day by combined treatment with phosphate and cinacalcet. Serum measurements of ionized calcium (Ca), phosphate, creatinine, intact PTH, 1,25(OH)2D, FGF23, and tubular threshold for phosphate/glomerular filtration rate (TP/GFR) were assessed in response to short-term treatment with phosphate and cinacalcet and compared with long-term administration of phosphate and calcitriol. Results: Oral phosphate load increased serum phosphate, decreased ionized calcium, and increased PTH. Twenty-four hours later, FGF23 significantly increased and 1,25(OH)2D decreased. The concomitant administration of phosphate and cinacalcet resulted in further decrease in serum Ca2+ but suppression of PTH and greater increase in serum phosphate and TP/GFR. Chronic treatment with phosphate and calcitriol resulted in a smaller increment in serum phosphate and high serum FGF23. Conclusions: Traditional therapy of XLH with phosphate and calcitriol elevates FGF23 and has the potential to stimulate PTH. Short-term treatment with cinacalcet suppresses PTH, leading to increase in TP/GFR and serum phosphate. Thus, long-term clinical studies are needed to investigate whether cinacalcet may be a useful adjuvant in the treatment of XLH, allowing the use of lower doses of phosphate and calcitriol.
-
Hypertension in Hypophosphatemic Rickets--role of secondary hyperparathyroidism.
Pediatric nephrology (Berlin Germany), 2003Co-Authors: Uri Alon, Roshanak Monzavi, Marc R. Lilien, Majid Rasoulpour, Mitchell E. Geffner, Ora YadinAbstract:Hypertension has been anecdotally reported in children with Familial Hypophosphatemic Rickets (XLH). To better identify and characterize the clinical and laboratory features of hypertensive XLH children, we reviewed the medical records of 41 XLH children, all treated with phosphate and vitamin D analogues. Eight children, who were originally normotensive, developed hypertension during the 2nd decade of life. At diagnosis of hypertension all had persistent secondary/tertiary hyperparathyroidism (HPTD), defined as high serum parathyroid hormone (PTH) for 12 months or longer. Seven had nephrocalcinosis (NC). Analysis of data showed that of 11 children with HPTD, 8 developed hypertension compared with 0 among 30 without HPTD (P
-
Effect of Acid-Phosphate Vs Neutral-Phosphate on Urine Acidity, Acid-Base Balance and Mineral Homeostasis in Children with Familial Hypophosphatemic Rickets (XLH)
Pediatric Research, 1999Co-Authors: Uri Alon, Wayne V. Moore, I. David SchwartzAbstract:Effect of Acid-Phosphate Vs Neutral-Phosphate on Urine Acidity, Acid-Base Balance and Mineral Homeostasis in Children with Familial Hypophosphatemic Rickets (XLH)
Ronald Rosenfeld - One of the best experts on this subject based on the ideXlab platform.
-
Growth Hormone Therapy in Hypophosphatemic Rickets
JAMA Pediatrics, 1991Co-Authors: Darrell M. Wilson, Edward O. Reiter, Valerie E. Quarmby, Joseph M Gertner, Alan H Morris, Robert Marcus, Ronald RosenfeldAbstract:• The effects of growth hormone therapy on the biochemical measures of bone metabolism were studied in 11 children aged 3.5 to 17 years who had Familial Hypophosphatemic Rickets; five were male. Subjects were maintained on a regimen of stable doses of conventional therapy (calcitriol and phosphate). Subjects were studied at baseline receiving conventional therapy and during three sequential treatment periods: no therapy (4 weeks), growth hormone only (0.05 mg/kg per day for 4 weeks), and conventional therapy plus growth hormone (2 weeks). The nine youngest subjects were continued on a regimen of triple therapy for an additional 24 weeks. Serum phosphate averaged 0.93±0.13 mmol/L (mean±SD) at entry and decreased when the subjects were not receiving any therapy. During the 4 weeks of growth hormone only treatment, phosphate rose in all 11 subjects (0.70±0.08 mmol/L to 0.83±0.08 mmol/L). With triple therapy, phosphate remained higher than with no therapy. Calcitriol, osteocalcin, and parathyroid hormone increased as the subjects received growth hormone alone. Insulinlike growth factor I z scores rose significantly in response to growth hormone therapy alone. All nine subjects receiving 6 months of triple therapy increased their growth rate z scores. Exogenous growth hormone therapy may be useful in Familial Hypophosphatemic Rickets. ( AJDC . 1991;145:1165-1170)
D Septier - One of the best experts on this subject based on the ideXlab platform.
-
Dentin Noncollagenous Matrix Proteins in Familial Hypophosphatemic Rickets
Cells tissues organs, 2008Co-Authors: Celine Gaucher, Frederic Jehan, D Septier, Matthew Garabedian, Tchilalo Boukpessi, Peter S.n. Rowe, Michel E. Goldberg, Catherine Chaussain-millerAbstract:Familial Hypophosphatemic Rickets is transmitted in most cases as an X-linked dominant trait and results from the mutation of the PHEX gene predominantly expressed in osteoblast and odontoblast. Patients with Rickets have been reported to display important dentin defects. Our purpose was to explore the structure, composition and distribution of noncollagenous proteins (NCPs) of Hypophosphatemic dentin. We collected teeth from 10 Hypophosphatemic patients whose mineralization occurred either in a Hypophosphatemic environment or in a corrected phosphate and vitamin environment. Teeth were examined by scanning electron microscopy, immunohistochemistry and Western blot analysis. An abnormal distribution (accumulation in interglobular spaces) and cleavage of the NCPs and particularly of matrix extracellular phosphoglycoprotein were observed in deciduous dentin. In contrast, it was close to normal in permanent dentin mineralized under corrected conditions. In conclusion, dentin mineralization in a corrected phosphate and vitamin D environment compensates the adverse effect of PHEX mutation.
-
dentin structure in Familial Hypophosphatemic Rickets benefits of vitamin d and phosphate treatment
Oral Diseases, 2007Co-Authors: C Chaussainmiller, Charlotte Sinding, D Septier, Maryse Wolikow, Michel Goldberg, Matthew GarabedianAbstract:Objective: To evaluate the outcome of 1-(OH) vitamin D and oral phosphate treatment on dentin structure in patients with Familial Hypophosphatemic Rickets, and expression of SIBLINGs (a family of non-collagenous proteins involved in dentinogenesis) and osteocalcin. Patients and methods: Seven patients with Familial Hypophosphatemic Rickets (age 3–16 years) were studied before or during treatment. Deciduous and permanent teeth were prepared for scanning electron microscopy (SEM) analysis and immunohistochemistry. Results: Untreated or inadequately treated patients had necrotic teeth with impaired dentin mineralization including unmerged calcospherites and accumulation of non-collagenous proteins in wide interglobular spaces. Most of the primary incisors analyzed displayed fissures linking enamel subsurface to pulp horn. These elements may explain the bacterial penetration and dental abscesses despite the absence of carious lesions. Well-treated patients had healthy teeth with good dentin mineralization and little evidence of calcospherites. Conclusion: Treatment of Hypophosphatemic children with 1-(OH) vitamin D and oral phosphate insures good dentin development and mineralization, and prevents clinical anomalies such as the dental necrosis classically associated with the disease. Starting treatment during early childhood and good adherence to the therapy are mandatory to observe these beneficial effects.
-
Dentin Alteration of Deciduous Teeth in Human Hypophosphatemic Rickets
Calcified Tissue International, 2006Co-Authors: Tchilalo Boukpessi, D Septier, Matthew Garabedian, S. Bagga, M. Goldberg, Catherine Chaussain-millerAbstract:Familial Hypophosphatemic Rickets is in most cases transmitted as an X-linked dominant trait and results from mutation of the PHEX gene, predominantly expressed in osteoblast and odontoblast. Patients have been reported to display important dentin defects, and therefore, we explored the dentin structure, composition, and distribution of extracellular matrix (ECM) molecules in Hypophosphatemic human deciduous teeth. Compared to age-matched controls, the dentin from Hypophosphatemic patients exhibited major differences: presence of large interglobular spaces resulting from the lack of fusion of calcospherites in the circumpulpal dentin; defective mineralization in the interglobular spaces contrasting with normal Ca-P levels in the calcospherites on X-ray microanalysis; abnormal presence of low-molecular weight protein complexes recognized on Western blots by antibodies against matrix extracellular phosphoglycoprotein (MEPE), dentin sialoprotein, osteopontin, and reduced osteocalcin (OC) level; and accumulation in the interglobular spaces of immunolabeling with antibodies against DSP, dentin matrix protein, bone sialoprotein, MEPE and OC, while chondroitin/dermatan sulfate glycosaminoglycans were exclusively located inside calcospherites. Alterations of the post-translational processing or partial degradation of some ECM appear as key factors in the formation of the defective Hypophosphatemic dentin.
Celine Gaucher - One of the best experts on this subject based on the ideXlab platform.
-
Familial Hypophosphatemic vitamin d resistant Rickets prevention of spontaneous dental abscesses on primary teeth a case report
Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 2009Co-Authors: Diane Douyere, Celine Gaucher, C Joseph, Catherine Chaussain, F CoursonAbstract:Familial Hypophosphatemic vitamin D-resistant Rickets is a hereditary disease generally transmitted as an X-linked dominant trait and characterized by distinctive general clinical signs. Dental features include spontaneous dental abscesses that occur in the absence of a history of trauma or dental decay. The challenge for the dentist is to prevent and treat these lesions. This report describes the case of a young Hypophosphatemic boy with abscesses. In this case, the application of fluid resin composites with a self-etching primer bonding system to all primary teeth prevented abscess formation for more than 1 year and thus avoided endodontic treatment or extraction. This constitutes a new approach to the prevention of spontaneous abscesses on primary teeth in children with Familial Hypophosphatemic Rickets.
-
phex analysis in 118 pedigrees reveals new genetic clues in Hypophosphatemic Rickets
Human Genetics, 2009Co-Authors: Celine Gaucher, Odile Walrantdebray, Thyminh Nguyen, Laure Esterle, Matthew Garabedian, Frederic JehanAbstract:Familial Hypophosphatemic Rickets is a rare disease, which is mostly transmitted as an X-linked dominant trait, and mutations on the phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) gene are responsible for the disease in most Familial cases. In this study we analyzed PHEX in a large cohort of 118 pedigrees representing 56 Familial cases and 62 sporadic cases. The high-resolution melting curves technique was tested as a screening method, along with classical sequencing. PHEX mutations have been found in 87% of Familial cases but also in 72% of sporadic cases. Missense mutations were found in 16 probands, two of which being associated with other PHEX mutations resulting into truncated proteins. By plotting missense mutations described so far on a 3D model of PHEX we observed that these mutations focus on two regions located in the inner part of the PHEX protein. Family members of 13 sporadic cases were analyzed and a PHEX mutation was detected in one of the apparently healthy mother. These results highlight the major role of PHEX in X-linked dominant Hypophosphatemic Rickets, and give new clues regarding the genetic analysis of the disease. A screening of the different family members should be mandatory when a PHEX mutation is assessed in a sporadic case and the search for another PHEX mutation should be systematically proceed when facing a missense mutation.
-
Dentin Noncollagenous Matrix Proteins in Familial Hypophosphatemic Rickets
Cells tissues organs, 2008Co-Authors: Celine Gaucher, Frederic Jehan, D Septier, Matthew Garabedian, Tchilalo Boukpessi, Peter S.n. Rowe, Michel E. Goldberg, Catherine Chaussain-millerAbstract:Familial Hypophosphatemic Rickets is transmitted in most cases as an X-linked dominant trait and results from the mutation of the PHEX gene predominantly expressed in osteoblast and odontoblast. Patients with Rickets have been reported to display important dentin defects. Our purpose was to explore the structure, composition and distribution of noncollagenous proteins (NCPs) of Hypophosphatemic dentin. We collected teeth from 10 Hypophosphatemic patients whose mineralization occurred either in a Hypophosphatemic environment or in a corrected phosphate and vitamin environment. Teeth were examined by scanning electron microscopy, immunohistochemistry and Western blot analysis. An abnormal distribution (accumulation in interglobular spaces) and cleavage of the NCPs and particularly of matrix extracellular phosphoglycoprotein were observed in deciduous dentin. In contrast, it was close to normal in permanent dentin mineralized under corrected conditions. In conclusion, dentin mineralization in a corrected phosphate and vitamin D environment compensates the adverse effect of PHEX mutation.