Dinucleotide repeat polymorphism at the DXS1683 locus

Econs, Michael J.; Francis, Fiona; Rowe, Peter; Speer, Marcy C.; O’Riordan, J. L. H.; Lehrach, Hans; Becker, P. A.

doi:10.1093/hmg/3.4.680

Cited by 22 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Family members were genotyped for five microsatellite polymorphisms, closely linked to the CLS locus, (DXS443, DXS999, DXS1229, DXS365 and DXS1683) as previously reported. 13,14 The results of haplotype analysis are shown in Figure 4: microsatellites DXS 1683 and DXS 999, flanking the CLS locus proximally and distally respectively, were informative. The patient and his three half sisters all had inherited the same haplotype from their mother.…”

Section: Resultsmentioning

confidence: 99%

Germline mosaicism in Coffin-Lowry syndrome

et al. 1998

View full text Add to dashboard Cite

We have identified a Coffin-Lowry syndrome pedigree where the disorder is associated with a novel splice site mutation in the RSK2 gene, leading to in-phase skipping of exon 5. Western blot analysis, using an antibody directed against the C-terminus of RSK2, failed to reveal RSK2 in this patient, suggesting strongly that the resulting internally deleted protein is unstable. The mutation was present in the DNA of one affected son and one manifesting daughter but was absent in two asymptomatic daughters, who carry the at-risk haplotype, and in the mother's somatic cell (lymphocyte) DNA. The results are consistent with the mutation arising as a postzygotic event in the mother, who therefore is a germinal mosaic. The application of linked markers to identify the disease allele for conventional genetic counselling would have been misleading in this family. This observation again highlights the importance of precise identification of the disease-causing mutation.

show abstract

Section: Resultsmentioning

confidence: 99%

Germline mosaicism in Coffin-Lowry syndrome

et al. 1998

View full text Add to dashboard Cite

show abstract

“…Subsequent investigations resulted in cloning and identification of the disease gene as PHEX , a PH osphate regulating gene with homologies to E ndopeptidases located on the X -chromosome [36], [37], [38], [39], [40] and [41]. The gene encodes a 749-amino acid protein, consisting of a small aminoterminal intracellular tail, a single, short transmembrane peptide, and a large carboxyterminal extracellular peptide with a motif typical of zinc metalloproteases.…”

Section: X-linked Hypophosphatemic Ricketsmentioning

confidence: 99%

Osteocyte regulation of phosphate homeostasis and bone mineralization underlies the pathophysiology of the heritable disorders of rickets and osteomalacia

Feng

Clinkenbeard

Yuan

et al. 2013

Bone

View full text Add to dashboard Cite

Although recent studies have established that osteocytes function as secretory cells that regulate phosphate metabolism, the biomolecular mechanism(s) underlying these effects remain incompletely defined. However, investigations focusing on the pathogenesis of X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), and autosomal recessive hypophosphatemic rickets (ARHR), heritable disorders characterized by abnormal renal phosphate wasting and bone mineralization, have clearly implicated FGF23 as a central factor in osteocytes underlying renal phosphate wasting, documented new molecular pathways regulating FGF23 production, and revealed complementary abnormalities in osteocytes that regulate bone mineralization. The seminal observations leading to these discoveries were the following: 1) mutations in FGF23 cause ADHR by limiting cleavage of the bioactive intact molecule, at a subtilisin-like protein convertase (SPC) site, resulting in increased circulating FGF23 levels and hypophosphatemia; 2) mutations in DMP1 cause ARHR, not only by increasing serum FGF23, albeit by enhanced production and not limited cleavage, but also by limiting production of the active DMP1 component, the C-terminal fragment, resulting in dysregulated production of DKK1 and β-catenin, which contributes to impaired bone mineralization; and 3) mutations in PHEX cause XLH both by altering FGF23 proteolysis and production and causing dysregulated production of DKK1 and β-catenin, similar to abnormalities in ADHR and ARHR, but secondary to different central pathophysiological events. These discoveries indicate that ADHR, XLH, and ARHR represent three related heritable hypophosphatemic diseases that arise from mutations in, or dysregulation of, a single common gene product, FGF23 and, in ARHR and XLH, complimentary DMP1 and PHEX directed events that contribute to abnormal bone mineralization.

show abstract

“…In 1995, the HYP consortium discovered a new gene PHEX (previously known as PEX) and identified its primary role in X-linked hypophosphatemic rickets (HYP also known as XLH) 9, 13–24 . Pictures of the “ first ” human XLH patient shown to have a mutation in the PHEX gene and the human murine-homolog of the disease are shown in Figure 2.…”

Section: Phex Its Physiological Substrate (Asarm Peptide) Osteomentioning

confidence: 99%

“…PHEX, ITS PHYSIOLOGICAL SUBSTRATE (ASARM PEPTIDE), OSTEOMALACIA AND HYPOPHOSPHATEMIC RICKETS In 1995, the HYP consortium discovered a new gene, PHEX (previously known as PEX), and identified its primary role in X-linked hypophosphatemic rickets (HYP also known as XLH). 9,[13][14][15][16][17][18][19][20][21][22][23][24] Pictures of the 'first' human XLH patient shown to have a mutation in the PHEX gene and the human murine homolog of the disease are shown in Figure 2. Following this MEPE was cloned as a phosphaturic factor expressed from the tumour of a patient with tumour-induced osteomalacia (TIO).…”

Section: Introduction: Back To the Futurementioning

confidence: 99%

The chicken or the egg: PHEX, FGF23 and SIBLINGs unscrambled

Rowe

2012

Cell Biochemistry & Function

View full text Add to dashboard Cite

The eggshell is an ancient innovation that helped the vertebrates’ transition from the oceans and gain dominion over the land. Coincident with this conquest several new eggshell and noncollagenous bone-matrix proteins (NCPs) emerged. The protein ovocleidin-116 is one of these proteins with an ancestry stretching back to the Triassic. Ovocleidin-116 is an avian homolog of Matrix Extracellular Phosphoglycoprotein (MEPE) and belongs to a group of proteins called Small Integrin-Binding Ligand Interacting Glycoproteins (SIBLINGs). The genes for these NCPs are all clustered on chromosome 5q in mice and chromosome 4q in humans. A unifying feature of the SIBLING proteins is an Acidic Serine Aspartate Rich MEPE associated motif (ASARM). The ASARM motif and the released ASARM peptide play roles in mineralization, bone turnover, mechanotransduction, phosphate regulation and energy metabolism. ASARM peptides and motifs are physiological substrates for PHEX, a Zn metalloendopeptidase. Defects in PHEX are responsible for X-linked hypophosphatemic rickets. PHEX interacts with another ASARM motif containing SIBLING protein, Dentin Matrix Protein-1 (DMP1). DMP1 mutations cause bone-renal defects that are identical with the defects caused by loss of PHEX function. This results in autosomal recessive hypophosphatemic rickets (ARHR). In both XLH and ARHR increased FGF23 expression occurs and activating mutations in FGF23 cause autosomal dominant hypophosphatemic rickets (ADHR). ASARM peptide administration in vitro and in vivo also induces increased FGF23 expression. This review will discuss the evidence for a new integrative pathway involved in bone formation, bone-renal mineralization, renal phosphate homeostasis and energy metabolism in disease and health.

show abstract

Dinucleotide repeat polymorphism at the DXS1683 locus

Cited by 22 publications

References 0 publications

Germline mosaicism in Coffin-Lowry syndrome

Germline mosaicism in Coffin-Lowry syndrome

Osteocyte regulation of phosphate homeostasis and bone mineralization underlies the pathophysiology of the heritable disorders of rickets and osteomalacia

The chicken or the egg: PHEX, FGF23 and SIBLINGs unscrambled

Contact Info

Product

Resources

About