Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EXOSTOSES, MULTIPLE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed1998

The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate.

Hereditary multiple exostoses, characterized by multiple cartilaginous tumors, is ascribed to mutations at three distinct loci, denoted EXT1-3. Here, we report the purification of a protein from bovine serum that harbored the D-glucuronyl (GlcA) and N-acetyl-D-glucosaminyl (GlcNAc) transferase activities required for biosynthesis of the glycosaminoglycan, heparan sulfate (HS). This protein was identified as EXT2. Expression of EXT2 yielded a protein with both glycosyltransferase activities. Moreover, EXT1, previously found to rescue defective HS biosynthesis (McCormick, C., Leduc, Y., Martindale, D., Mattison, K., Esford, L. E., Dyer, A. P., and Tufaro, F. (1998) Nat. Genet. 19, 158-161), was shown to elevate the low GlcA and GlcNAc transferase levels of mutant cells. Thus at least two members of the EXT family of tumor suppressors encode glycosyltransferases involved in the chain elongation step of HS biosynthesis.

Amino Acid Sequence↗
PubMed2000

[Ulnar lengthening in osteochondroma (multiple cartilagenous exostoses) of the forearm].

The osteochondroma is the most frequent bone tumor to occur during the period of growth. The multiple hereditary form often involves the forearms. Depending on localisation and size of the tumor, shortening of the bones in the forearm, angular malalignments and functional impairment of the wrist and elbow joints may result. Early diagnosis and surgery in the growing child can prevent these complications. 13 children were operated on altogether 15 forearms. In nine cases lengthening of the ulna was necessary to correct ulnar instability of the wrist as well as improving the support of the carpus and preventing dislocation of the radial head.

Adolescent↗
PubMed1993

Multiple hereditary exostoses. An epidemiologic study of an isolated community in Manitoba.

From 1986 through 1988, 266 persons (149 adults and 117 children) were screened for multiple hereditary exostosis (MHE) in an isolated northern Ojibway community. Physical examination and confirmation by roentgenogram skeletal survey disclosed 21 children (19.4%) and 14 adults (9.5%) affected with MHE. Forty-one percent of children had lesions detectable before ten years of age, some as early as two years of age. Seventy-four percent of the lesions were characteristically sessile. Although lesions about the knee were most common, sites previously thought to be uncommon such as the metatarsals, hand, and spine were involved in 40% of the children. No cases of malignant degeneration have occurred in the adult population. Severity and multiplicity of lesions in successive generations point to an oncogenic gene origin. This study shows striking variance from current literature and provides a unique and valuable baseline assessment of research on the cause and natural history of MHE.

Adolescent↗
PubMed1991

[A case of pneumothorax in a patient with costal exostosis].

A 21-year-old male was admitted to our hospital complaining of chest pain. He had undergone operations on multiple exostoses of his lower extremities when he was thirteen and fifteen years old. Family history revealed multiple exostoses in his mother and one of his cousins. Chest roentgenograms showed right pneumothorax and a mass arising from the seventh rib in the right lower lung filed. Chest CT revealed that the mass was located in thorax but outside the lung. These findings suggested that the pneumothorax was secondary to the injury of the right lung caused by an exostosis arising from the rib. Upon operation, we found a laceration of the lower lobe and a hard mass the size of a pea protruding from the seventh rib. A small bony spicule was also found to be projecting from the sixth rib. The hard mass and the spicule were resected with a normal portion of the seventh and the sixth ribs. The pathological findings of these bony lesion proved to be consistent with exostosis. The patient's postoperative course was uneventful. This case of pneumothorax caused by an exostosis lacerating the lung is rare.

Adult↗
PubMed1997

Identification of novel mutations in the human EXT1 tumor suppressor gene.

Hereditary multiple exostoses (EXT) is a genetically heterogeneous bone disorder caused by genes segregating on human chromosomes 8, 11, and 19 and designated EXT1, EXT2 and EXT3, respectively. Recently, the EXT1 gene has been isolated and partially characterized and appears to encode a tumor suppressor gene. We have identified six mutations in the human EXT1 gene from six unrelated multiple exostoses families segregating for the EXT gene on chromosome 8. One of the mutations we detected is the same 1-bp deletion in exon 6 that was previously reported in two independent EXT families. The other five mutations, in exons 1, 6, 9, and the splice junction at the 3' end of exon 2, are novel. In each case, the mutation is likely to result in a truncated or nonfunctional EXT1 protein. These results corroborate and extend the previous report of mutations in this gene in two EXT families, and provide additional support for the EXT1 gene as the cause of hereditary multiple exostoses in families showing linkage to chromosome 8.

Alternative Splicing↗
PubMed1998

[Vertebral body exocytosis and spinal cord compression].

Osteochondroma is a cartilaginous tumor, the most common benign tumor of bone. It may involve solitary or multiple exostoses (or osteochondromatosis) usually in hereditary multiple exostosis. The authors report a case of 13-year-old girl with a family history of hereditary multiples exostoses who presented with bilateral sciatica and cauda equina compression. The MRI showed a tumor of the L1 vertebral body. After surgery, pathologic specimens revealed the lesion to be an osteochondroma. Involvement of the vertebral column has been estimated from 1.3 to 4%. Spinal cord compression is rare. CT provides the analysis of the components of the tumor and clearly demonstrates it's intracanalar extension. MRI is superior in visualizing spinal cord compression. The prognosis is favorable after a surgical decompression.

Adolescent↗
PubMed1998

[Hereditary exostoses--presentation of a family case].

In this article we present a Norwegian family with hereditary multiple exostoses and a review of relevant literature. 21 family members were examined; ten males and six females had multiple exostoses, the youngest from six months of age. The exostoses had led to compression of nerves, disturbance of bone growth with shortening and bowing of the forearm bones, and valgus deformity of the knee and ankle. Physical function and quality of life was generally well preserved. Contrary to most reports, nearly half of the patients had allegedly noticed growth or debut of exostoses in adulthood. Almost half of the patients had had the exostoses removed surgically twice, (median value). Malignant transformation of exostoses has not been observed in the family.

Adolescent↗
PubMed2001

A novel deletion mutation of the EXT2 gene in a large Chinese pedigree with hereditary multiple exostosis.

Hereditary multiple exostoses (EXT) is an autosomal dominant disease characterized by the formation of cartilage-capped prominences (exostoses) that develop from the juxta-epiphyseal regions of the long bones. 3 genes are known to be involved in the formation of exostoses. Among them, EXT1 and EXT2, which encode enzymes that catalyse the biosynthesis of heparan sulfate, an important component of the extracellular matrix, are responsible for over 70% of the EXT cases. A large Chinese family with hereditary multiple exostoses has been analysed and the disease-causing mutation has been found. Blood samples were obtained from 69 family members, including 23 affected individuals. The EXT phenotype was shown to be linked to the EXT2 gene by using 2-point linkage analysis. After polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis and DNA sequencing, a previously unreported deletion of a G in exon 3 of EXT2 gene was observed. This deletion co-segregated with the disease phenotype, suggesting that it is the disease-causing mutation in this family. Furthermore, in at least 4 members chondrosarcoma occurred after either an operation or injury of the exostosis and 3 of them died of the malignancy in the family. Whether the operation or injury was responsible for the malignant transformation still needs further study.

Base Sequence↗
PubMed2005

Combination of WAGR and Potocki-Shaffer contiguous deletion syndromes in a patient with an 11p11.2-p14 deletion.

Aniridia, Wilms tumor, genitourinary abnormalities, growth and mental retardation are the cardinal features of the WAGR 11p13 deletion syndrome. The Potocki-Schaffer syndrome or proximal 11p deletion syndrome (previously DEFECT11 syndrome) is a contiguous gene syndrome associated with deletions in 11p11.2, principal features of which are multiple exostoses and enlarged parietal foramina. Mental handicap, facial dysmorphism and craniosynostosis may also be associated. We report a patient with combined WAGR and Potocki-Shaffer syndromes, and obesity. She presented with aniridia, cataract, nystagmus, corneal ulcers and bilateral congenital ptosis. A left nephroblastoma was detected at 15 months. Other features included moderate developmental delay, growth deficiency, facial dysmorphism, multiple exostoses and cranial lacunae. High-resolution and molecular cytogenetics confirmed a del(11)(p11.2p14.1) deletion with a proximal breakpoint between the cosmid DO8153 and the BAC RP11-104M24 to a distal breakpoint between cosmids CO8160 (D11S151) and F1238 (D11S1446). The deletion therefore includes EXT2, ALX4, WT1 and PAX6. This case appears to be the second patient reported with this combined deletion syndrome and confirms the association of obesity in the WAGR spectrum, a feature previously reported in four cases, and for which the acronym WAGRO has been suggested. Molecular and follow-up data on the original WAGRO case are briefly presented.

Adolescent↗
PubMed1992

Metachondromatosis: a report of two cases in a family.

We have described a 10-year-old Japanese boy and his father with metachondromatosis characterized by multiple exostoses, enchondromas, and periarticular calcification or ossification and reviewed the literature on this condition. The boy developed bilateral epiphyseal changes in the hips mimicking Perthes' disease. These cases are the first Japanese individuals with this disorder. The natural history and the associated disorders of metachondromatosis are also discussed in this paper. Metachondromatosis is an inherited skeletal dysplasia characterized by multiple cartilaginous exostoses, multiple enchondromas, and periarticular calcification or ossification. The mode of inheritance of the disease is autosomal dominant. In 1971, Maroteaux first described the disorder in 6 patients of 2 kindreds. Since then, 22 cases have been reported. However, no Japanese patient with this disorder has been described to date. We herein report a Japanese boy and his father with this rare bone dysplasia. The boy developed bilateral epiphyseal lesions in the femoral heads mimicking Perthes' disease.

Adult↗
PubMed1988

A clinicopathologic study of bony spurs on the pes anserinus.

Nineteen cases of exostoses located on part of the pes anserinus were studied clinically and histologically. All lesions were resected during surgery between 1965 and 1985. In these 19 cases, 14 had involvement of the tibia only at the insertion of the pes anserinus. Five had multiple exostoses with pes anserinus involvement. All exostoses occurring only in pes anserinus showed an icicle appearance in roentgenography and had no detectable cartilage cap. On the other hand, exostoses in patients with multiple exostoses (osteochondromas) showed varying appearances in roentgenography and had cartilage caps on their surfaces. Exostoses occurring only in the pes anserinus may or may not be osteochondromata and could be classified as pes anserinus bony spurs.

Adolescent↗
PubMed2000

Location of the glucuronosyltransferase domain in the heparan sulfate copolymerase EXT1 by analysis of Chinese hamster ovary cell mutants.

Heparan sulfate formation occurs by the copolymerization of glucuronic acid (GlcA) and N-acetylglucosamine (GlcNAc) residues. Recent studies have shown that these reactions are catalyzed by a copolymerase encoded by EXT1 and EXT2, members of the exostosin family of putative tumor suppressors linked to hereditary multiple exostoses. Previously, we identified a collection of Chinese hamster ovary cell mutants (pgsD) that failed to make heparan sulfate (Lidholt, K., Weinke, J. L., Kiser, C. S., Lugemwa, F. N., Bame, K. J., Cheifetz, S., Massagué, J., Lindahl, U., and Esko, J. D. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 2267-2271). Here, we show that pgsD mutants contain mutations that either alter GlcA transferase activity selectively or that affect both GlcNAc and GlcA transferase activities. Expression of EXT1 corrects the deficiencies in the mutants, whereas EXT2 and the related EXT-like cDNAs do not. Analysis of the EXT1 mutant alleles revealed clustered missense mutations in a domain that included a (D/E)X(D/E) motif thought to bind the nucleotide sugar from studies of other transferases. These findings provide insight into the location of the GlcA transferase subdomain of the enzyme and indicate that loss of the GlcA transferase domain may be sufficient to cause hereditary multiple exostoses.

Acetylglucosamine↗
PubMed2004

Ext1-dependent heparan sulfate regulates the range of Ihh signaling during endochondral ossification.

Exostosin1 (Ext1) belongs to a family of glycosyltransferases necessary for the synthesis of the heparan sulfate (HS) chains of proteoglycans, which regulate signaling of several growth factors. Loss of tout velu (ttv), the homolog of Ext1 in Drosophila, inhibits Hedgehog movement. In contrast, we show that reduced HS synthesis in mice carrying a hypomorphic mutation in Ext1 results in an elevated range of Indian hedgehog (Ihh) signaling during embryonic chondrocyte differentiation. Our data suggest a dual function for HS: First, HS is necessary to bind Hedgehog in the extracellular space. Second, HS negatively regulates the range of Hedgehog signaling in a concentration-dependent manner. Additionally, our data indicate that Ihh acts as a long-range morphogen, directly activating the expression of parathyroid hormone-like hormone. Finally, we propose that the development of exostoses in the human Hereditary Multiple Exostoses syndrome can be attributed to activation of Ihh signaling.

Animals↗
PubMed2005

Construction of a natural panel of 11p11.2 deletions and further delineation of the critical region involved in Potocki-Shaffer syndrome.

Potocki-Shaffer syndrome (PSS) is a contiguous gene deletion syndrome that results from haploinsufficiency of at least two genes within the short arm of chromosome 11[del(11)(p11.2p12)]. The clinical features of PSS can include developmental delay, mental retardation, multiple exostoses, parietal foramina, enlarged anterior fontanel, minor craniofacial anomalies, ophthalmologic anomalies, and genital abnormalities in males. We constructed a natural panel of 11p11.2-p13 deletions using cell lines from 10 affected individuals, fluorescence in situ hybridization (FISH), microsatellite analyses, and array-based comparative genomic hybridization (array CGH). We then compared the deletion sizes and clinical features between affected individuals. The full spectrum of PSS manifests when deletions are at least 2.1 Mb in size, spanning from D11S1393 to D11S1385/D11S1319 (44.6-46.7 Mb from the 11p terminus) and encompassing EXT2, responsible for multiple exostoses, and ALX4, causing parietal foramina. Yet one subject with parietal foramina whose deletion does not include ALX4 indicates that ALX4 in this subject may be rendered functionally haploinsufficient by a position effect. Based on comparative deletion mapping of eight individuals with the full PSS syndrome including mental retardation and two PSS families with no mental retardation, at least one gene related to mental retardation is likely located between D11S554 and D11S1385/D11S1319, 45.6-46.7 Mb from the 11p terminus.

Abnormalities, Multiple↗
PubMed1986

[Valgus deformities of the ankle in children].

In children valgus deformities of the ankle joint are usually due to neurological conditions (spina bifida, poliomyelitis, spasticity). The deformity is characterized by a shortened fibula, wedging of distal tibial epiphysis and valgus tilt of the talus. Other conditions producing similar deformity include congenital and acquired fibular pseudarthroses, multiple exostoses and some cases of tarsal synostosis. Early treatment of a progressive valgus in multiple exostoses is mandatory. The author describes a case of ankle valgus following an undiagnosed traumatic section of tibialis posterior tendon. After predictable failure of a Grice procedure, a persisting good correction was obtained by fibula lengthening combined with talus reposition and fixation on os calcis.

Ankle Joint↗