Vitamin D-resistant rickets

Burnett, Charles H.; Dent, C. E.; Harper, Christine M.; Warland, Barbara J.

doi:10.1016/0002-9343(64)90085-3

Cited by 120 publications

(24 citation statements)

References 9 publications

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“…Statistically significant hypocalcemia also was present in all mutants within the same range (8.38-9.17 mg/dL) ( Table 1). The serum PO 4 and Ca 2+ levels found in Hyp/Y and Gy/Y mice were consistent with those previously reported (Eicher et al 1976;Lyon et al 1986). …”

Section: Serum Chemistrysupporting

confidence: 92%

“…Serum PO 4 and Ca 2+ levels were assessed at 6 weeks of age in Hyp/Y, Hyp-2J/Y, Hyp-Duk/ Y, Gy/Y males and same-sex littermate controls by using the Beckman Synchron CX5 DELTA System (Beckman Coulter, Inc.). All mutant males had serum PO 4 levels (2.95-4.45 mg/dL) significantly lower than controls (Table 1).…”

Section: Serum Chemistrymentioning

confidence: 99%

“…X-linked dominant hypophosphatemia (XLH) is the most frequently occurring familial form of hypophosphatemic rickets in humans with an incidence of 1 per 20,000 individuals (Burnett et al 1964;Tenenhouse 1999 …”

Section: Introductionmentioning

confidence: 99%

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New intragenic deletions in the Phex gene clarify X-linked hypophosphatemia-related abnormalities in mice

et al. 2004

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X-linked hypophosphatemic rickets (XLH) in humans is caused by mutations in the PHEX gene. Previously, three mutations in the mouse Phex gene have been reported: Phex Hyp , Gy, and Phex Ska1 . Here we report analysis of two new spontaneous mutations in the mouse Phex gene, Phex and Phex Hyp-Duk . Phex and Phex Hyp-Duk involve intragenic deletions of at least 7.3 kb containing exon 15, and 30 kb containing exons 13 and 14, respectively. Both mutations cause similar phenotypes in males, including shortened hind legs and tail, a shortened square trunk, hypophosphatemia, hypocalcemia, and rachitic bone disease. In addition, mice carrying the Phex Hyp-Duk mutation exhibit background-dependent variable expression of deafness, circling behavior, and cranial dysmorphology, demonstrating the influence of modifying genes on Phexrelated phenotypes. Cochlear cross-sections from Phex Hyp-2J /Y and Phex Hyp-Duk /Y males reveal a thickening of the temporal bone surrounding the cochlea with the presence of a precipitate in the scala tympani. Evidence of the degeneration of the organ of Corti and spiral ganglion also are present in the hearing-impaired Phex Hyp-Duk /Y mice, but not in the normal-hearing Phex Hyp-2J /Y mice. Analysis of the phenotypes noted in Phex Hyp-Duk /Y an Phex Hyp-2J /Y males, together with those noted in Phex Ska1 /Y and Phex Hyp /Y males, now allow XLH-related phenotypes to be separated from non-XLH-related phenotypes, such as those noted in Gy/Y males. Also, identification of the genetic modifiers of hearing and craniofacial dysmorphology in Phex Hyp-Duk / Y mice could provide insight into the phenotypic variation of XLH in humans.X-linked dominant hypophosphatemia (XLH) is the most frequently occurring familial form of hypophosphatemic rickets in humans with an incidence of 1 per 20,000 individuals (Burnett et al. 1964;Tenenhouse 1999 NIH-PA Author ManuscriptThe Hyp mutation is a spontaneous deletion that begins in exon 15 and extends through exons 16-22 (Strom et al. 1997) into downstream intergenic sequences (Sabbagh et al. 2002). The Ska1 mutation is a chemically induced point mutation in a splice donor site immediately following exon 8 (Carpinelli et al. 2002). The Gy mutation is a radiationinduced deletion that removes 160-190 kb, including exons 1-3 and the Sms (spermine synthase) gene (Lorenz et al. 1998;Strom et al. 1997). Given that the gyro deletion includes more than one gene, the previous allelic symbol Phex Gy is inadequate; this mutation is here renamed gyro deletion region, symbol Gy (Mouse Genome Database, http://www.informatics.jax.org). Because neither the Hyp nor Gy mutations is restricted to the Phex coding sequence, it has been problematic to assign a specific phenotype solely to the Phex gene.Here we report the identification of two new spontaneous intragenic deletions in the mouse Phex gene, hypophosphatemia-2 Jackson, symbolized Phex Hyp-2J (Hyp-2J) and hypophosphatemia-Duke, symbolized, Phex Hyp-Duk (Hyp-Duk). Mice carrying either mutation, together with those car...

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Section: Serum Chemistrysupporting

confidence: 92%

Section: Serum Chemistrymentioning

confidence: 99%

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New intragenic deletions in the Phex gene clarify X-linked hypophosphatemia-related abnormalities in mice

et al. 2004

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“…Ara, arabinose; aMM, a-methylmannoside; GlcNAc, N-acetylglucosamine; GaINAc, N-acetylgalactosamine; Thiogal, thiogalactoside; ,B-Lac, , 8- (15). Hypophosphatemia, on the other hand, elicits osteomalacia because the levels of circulating phosphorus are inadequate to support normal bone mineralization (16).…”

Section: Introductionmentioning

confidence: 99%

Defective binding of macrophages to bone in rodent osteomalacia and vitamin D deficiency. In vitro evidence for a cellular defect and altered saccharides in the bone matrix.

Bar‐Shavit¹,

Kahn²,

Teitelbaum³

1983

J. Clin. Invest.

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A B S T R A C T In the osteomalacic as well as normal skeleton, few osteoclasts are associated with osteoidcovered bone surfaces. The reason for this particular cellular deficit is not clear, but may relate to the inability of osteoclasts and/or osteoclast precursors (monocyte-macrophages) to attach to immature, unmineralized bone matrix, a step apparently essential for normal resorptive activity and osteoclast differentiation. In this study, we have examined cell-bone binding using macrophages (MO) and bone isolated from vitamin D-deficient rats and hypophosphatemic, osteomalacic mice and from their normal counterparts. The data show that MO-bone attachment is greatly reduced (P < 0.001) in both vitamin D deficiency and hypophosphatemia, but that the mechanisms responsible for this reduction are apparently different in the two disorders. In hypophosphatemia, the reduction in binding appears solely attributable to the absence or inaccessibility of bone matrix oligosaccharides or glycoproteins essential to the attachment process. In vitamin D deficiency, on the other hand, not only is the bone matrix defective as a binding substrate, but the MO, per se, is limited in its capacity to attach to normal, vitamin D-deficient, and hypophosphatemic bone.

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“…The hallmarks of this disease include a reduced serum concentration of inorganic phosphate (Pi) (1)(2)(3) and resistance to therapy with vitamin D (4)(5)(6). Current evidence suggests that the primary defect governing the genesis of XLH is an abnormality of Pi transport in the renal tubule (7).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a Role for 1,25-Dihydroxyvitamin D3 in the Pathogenesis and Treatment of X-linked Hypophosphatemic Rickets and Osteomalacia

et al. 1980

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Vitamin D-resistant rickets

Cited by 120 publications

References 9 publications

New intragenic deletions in the Phex gene clarify X-linked hypophosphatemia-related abnormalities in mice

New intragenic deletions in the Phex gene clarify X-linked hypophosphatemia-related abnormalities in mice

Defective binding of macrophages to bone in rodent osteomalacia and vitamin D deficiency. In vitro evidence for a cellular defect and altered saccharides in the bone matrix.

Evaluation of a Role for 1,25-Dihydroxyvitamin D3 in the Pathogenesis and Treatment of X-linked Hypophosphatemic Rickets and Osteomalacia

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