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Results for “EXOSTOSES, MULTIPLE”

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At least 667 records · Page 37Linked to original sources
PubMed1996

Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia.

Mutations in the diastrophic dysplasia sulfate transporter gene DTDST have been associated with a family of chondrodysplasias that comprises, in order of increasing severity, diastrophic dysplasia (DTD), atelosteogenesis type 2 (AO2), and achondrogenesis type 1B (ACG1B). To learn more about the molecular basis of DTDST chondrodysplasias and about genotype-phenotype correlations, we studied fibroblast cultures of three new patients: one with AO-2, one with DTD, and one with an intermediate phenotype (AO2/DTD). Reduced incorporation of inorganic sulfate into macromolecules was found in all three. Each of the three patients was found to be heterozygous for a c862t transition predicting a R279W substitution in the third extracellular loop of DTDST. In two patients (DTD and AO2/DTD), no other structural mutation was found, but polymerase chain reaction amplification and single-strand conformation polymorphism analysis of fibroblast cDNA showed reduced mRNA levels of the wild-type DTDST allele: these two patients may be compound heterozygotes for the "Finnish" mutation (as yet uncharacterized at the DNA level), which causes reduced expression of DTDST. The third patient (with AO2) had the R279W mutation compounded with a novel mutation, the deletion of cytosine 418 (delta c418), predicting a frameshift with premature termination. Also the delta c418 allele was underrepresented in the cDNA, in accordance with previous observations that premature stop codons reduce mRNA levels. The presence of the DTDST R279W mutation in a total of 11 patients with AO2 or DTD emphasizes the overlap between these conditions. This mutation has not been found so far in 8 analyzed ACG1B patients, suggesting that it allows some residual activity of the sulfate transporter.

Anion Transport Proteins↗
PubMed1999

Genes and chromosomal breakpoints in the Langer-Giedion syndrome region on human chromosome 8.

The tricho-rhino-phalangeal syndrome type II (TRPS II, or Langer-Giedion syndrome) is an example of contiguous gene syndromes, as it comprises the clinical features of two autosomal dominant diseases, TRPS I and a form of multiple cartilaginous exostoses caused by mutations in the EXT1 gene. We have constructed a contig of cosmid, lambda-phage, PAC, and YAC clones, which covers the entire TRPS I critical region. Using these clones we identified a novel submicroscopic deletion in a TRPS I patient and refined the proximal border of the minimal TRPS1 gene region by precisely mapping the inversion breakpoint of another patient. As a first step towards a complete inventory of genes in the Langer-Giedion syndrome chromosome region (LGCR) with the ultimate aim to identify the TRPS1 gene, we analyzed 23 human expressed sequence tags (ESTs) and four genes (EIF3S3, RAD21, OPG, CXIV) which had been assigned to human 8q24.1. Our analyses indicate that the LGCR is gene-poor, because none of the ESTs and genes map to the minimal TRPS1 gene region and only two of these genes, RAD21 and EIF3S3, are located within the shortest region of deletion overlap of TRPS II patients. Two genes, OPG and CXIV, which are deleted only in some patients with TRPS II may contribute to the clinical variability of this syndrome.

Child↗
PubMed2001

Cartilaginous lesions of bone.

Cartilaginous lesions of the skeleton are very unusual. It is extremely important to correlate the roentgenographic features, the clinical features, and the histological features to arrive at a definite diagnosis. Most cartilaginous lesions are benign or of low-grade malignancy. However, there are some subtypes of chondrosarcoma that behave in a highly aggressive fashion.

Bone Neoplasms↗
PubMed2005

EXT1 regulates chondrocyte proliferation and differentiation during endochondral bone development.

Multiple Hereditary Exostoses (MHE) is an autosomal dominant skeletal disorder most frequently caused by mutations in the EXT1 gene. MHE affects proper development of endochondral bones, such that all affected individuals present with exostoses adjacent to the growth plate of long bones, while some individuals exhibit additional bone deformities. EXT1 functions as a heparan sulfate (HS) co-polymerase, and when defective causes improper elongation of glycosaminoglycan side chains on core proteins of HS proteoglycans. Although analysis of heterozygous EXT1-deficient mice has failed to reveal any significant gross morphological variations in skeletal development, significant alterations in molecular signaling occur in the developing long bones. Our results indicate that defects in EXT1 and the resulting reduction in HS lead to enhanced Indian Hedgehog diffusion causing an increase in chondrocyte proliferation and delayed hypertrophic differentiation.

Animals↗
PubMed2004

Position of single amino acid substitutions in the collagen triple helix determines their effect on structure of collagen fibrils.

Collagen II fibrils are a critical structural component of the extracellular matrix of cartilage providing the tissue with its unique biomechanical properties. The self-assembly of collagen molecules into fibrils is a spontaneous process that depends on site-specific binding between specific domains belonging to interacting molecules. These interactions can be altered by mutations in the COL2A1 gene found in patients with a variety of heritable cartilage disorders known as chondrodysplasias. Employing recombinant procollagen II, we studied the effects of R75C or R789C mutations on fibril formation. We determined that both R75C and R789C mutants were incorporated into collagen assemblies. The effects of the R75C and R789C substitutions on fibril formation differed significantly. The R75C substitution located in the thermolabile region of collagen II had no major effect on the fibril formation process or the morphology of fibrils. In contrast, the R789C substitution located in the thermostable region of collagen II caused profound changes in the morphology of collagen assemblies. These results provide a basis for identifying pathways leading from single amino acid substitutions in collagen II to changes in the structure of individual fibrils and in the organization of collagenous matrices.

Binding Sites↗
PubMed1997

Exostosis of a rib causing laceration of the diaphragm: diagnosis and management.

A 17-year-old boy presented with spontaneous hemothorax due to a puncture wound of the diaphragm by an inward facing exostosis of the rib. Diagnosis was made by computed tomographic scan, and the patient underwent a video-assisted thoracoscopic procedure to remove the exostosis. This is only the eighth reported case of an exostosis causing hemothorax.

Adolescent↗
PubMed1983

A distinct chondrodysplasia resembling Kniest dysplasia: clinical, roentgenographic, histologic, and ultrastructural findings.

Two sibs, one girl and one boy, were observed in infancy with a severe lethal skeletal dysplasia syndrome that radiologically and histologically resembled Kniest dysplasia but clearly differed in clinical course and inheritance. Kniest dysplasia is a nonlethal syndrome, whereas both of these infants died in the neonatal period. Kniest dysplasia appears to be inherited as an autosomal dominant trait; the likely transmission in this family was autosomal recessive. Roentgenograms revealed dumbbell-shaped long bones superficially similar to Kniest dysplasia, but with markedly shortened diaphyses and metaphyseal irregularities. Chondro-osseous morphology demonstrated a superficially similar foamy "Swiss cheese" appearance to the cartilage matrix, as seen in Kniest dysplasia, but there were distinctly different changes in the growth plate and resting cartilage. Ultrastructurally, the chondrocytic endoplasmic reticulum was found to have an appearance different from that observed in either normal or Kniest cartilage. These cases likely represent a distinct chondrodysplasia.

Cartilage↗
PubMed1979

Differential diagnosis of cartilage tumors.

A total of 1187 cartilage tumors have been diagnosed at the Reference Center for Bone Tumors of the University of Freiburg; 67 of these were chondrosarcomas. All tumors were coded in terms of their frequency, age distribution, and localization. The typical radiographic, macroscopic, and histologic architecture is described for each tumor, and differential diagnostic aspects are described. Special attention is devoted to the distinction between proliferating chondromas and well-differentiated chondrosarcomas. which are often very difficult or even impossible to distinguish histologically. A grading system for chondrosarcomas is described. Cytophotometric DNA measurements may be applied to cartilage tumor cells in an effort to objectify the radiologic and histologic findings, and to make possible a decision between "benign" and "malignant". With the help of these modern histochemical methods it should be possible to solve differential diagnostic problems in cartilage tumors.

Cartilage Diseases↗
PubMed1998

[Activating mutations of the parathyroid hormone and parathyroid hormone related peptide].

Parathyroid hormone (PTH) and PTH related peptide (PTHrP) have a common main receptor: type I PTH-PTHrP receptor. PTH expresses its main metabolic actions, and PTHrP part of its autocrine or paracrine actions through this receptor. Jansen chondrodysplasia is a very rare disease mainly characterized by severe metaphyseal growth disorders leading to dwarfism and hypercalcemia. The group of Jüppner from the Massachusetts General Hospital in Boston recently demonstrated mutations on the gene of the type I PTH-PTHrP receptor in five patients with Jansen chondrodysplasia. These mutations result in permanent activation of the receptor responsible for the observed hypercalcemia and bone growth abnormalities due to the disease. Therefore Jansen chondrodysplasia appears as a remarkable clinical model outlining the major role of PTHrP in bone growth regulation.

Animals↗