Hereditary multiple exostoses: Confirmation of linkage to chromosomes 8 and 11

Blanton, Susan H.; Hogue, Deborah; Wagner, Michael J.; Wells, Dan E.; Young, Ian; Hecht, Jacqueline

doi:10.1002/(sici)1096-8628(19960315)62:2<150::aid-ajmg7>3.0.co;2-#

Cited by 21 publications

(5 citation statements)

References 13 publications

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“…Thus, the missense mutation identified cosegregated with the exostoses phenotype, suggesting that the mutation is the disease-causing one. Direct sequencing of 100 control chromosomes from unrelated and unaffected normal individuals did not reveal this missense mutation, thus excluding the possibility of a rare polymorphism, Analysis of EXT pedigrees has revealed that most are associated with EXT1 and EXT2 (Halloran-Blanton et al 1996;Raskind et al 1998), with EXT3 probably playing only a minor role. Our results provide further support for EXT1 and EXT2 genes being involved in EXT.…”

Section: Resultssupporting

confidence: 93%

“…Linkage analysis has demonstrated that EXT is caused by at least three different genes, EXT1 on chromosome 8q23-q24 (Cooke et al 1993), EXT2 on chromosome 11p11-p12 (Wu et al 1994;Wuyts et al 1995), and EXT3 on chromosome 19p (Le Merrer et al 1994). However, it now appears that most EXT families are linked to EXT1 and EXT2 loci (Halloran-Blanton et al 1996;Raskind et al 1998). Recently, the EXT1 and EXT2 genes have been cloned and germline mutations of these genes confirmed in EXT families (Ahn et al 1995;Stickens et al 1996;Wuyts et al 1996).…”

Section: Introductioncontrasting

confidence: 99%

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Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses

Park

Shin

Ku³

et al. 1999

J Hum Genet

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Hereditary multiple exostoses (EXT) is an autosomal dominantly inherited disease characterized by the formation of cartilage-capped prominences (exostoses) that develop from the juxtaepiphyseal regions of the long bones. Recently, EXT1 and EXT2 genes were cloned and germline mutations of EXT1 and EXT2 were identified in EXT families. In this study, we performed a mutational analysis of EXT1 and EXT2 genes in eight unrelated Korean EXT families by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis followed by direct DNA sequencing. As a result, we were able to identify one family (SNU-OC3) with the EXT1 mutation and another family (SNU-OC15) with the EXT2 mutation. The EXT1 mutation was a 10-bp deletion at the 3Ј end of exon 5 (CTAATTTAGg) including the splice site of this exon. The EXT2 mutation identified in the SNU-OC15 family was a missense mutation at codon 85 of exon 2 (TGC AE CGC), resulting in an amino acid change from cysteine to arginine. This missense mutation cosegregated with the disease phenotype in this family, suggesting that it is the diseasecausing mutation. These two mutations identified in EXT1 and EXT2 are novel ones.

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Section: Resultssupporting

confidence: 93%

Section: Introductioncontrasting

confidence: 99%

Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses

Park

Shin

Ku³

et al. 1999

J Hum Genet

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“…Cook et al (1993) provided evidence of linkage to chromosome 8 in 7 of their 11 families. Blanton et al (1996) mapped 6 of their 12 families to chromosome 8, and they mapped the remaining 6 families to the EXT2 locus at chromosome 11. A recent French study analyzed 29 smaller families and assigned 8 (28%) of them to the EXT1 locus, 5 (17%) to the EXT2 locus, and 3 (10%) to the EXT3 locus on chromosome 19p.…”

Section: Relative Proportion Of Ext1 To Ext2 Mutationsmentioning

confidence: 99%

“…In addition to the EXT1 gene on chromosome 8q23-q24 (Cook et al 1993) and the EXT2 gene on 11p11-p12 (Wu et al 1994;Wuyts et al 1995), linkage analysis has indicated the existence of a third gene (EXT3), on chromosome 19p (Le Merrer et al 1994). However, most EXT families appear to be linked to the EXT1 and EXT2 loci (Cook et al 1993;Blanton et al 1996;Legeai-Mallet et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Mutations in the EXT1 and EXT2 Genes in Hereditary Multiple Exostoses

Wuyts

Hul

Boulle

et al. 1998

The American Journal of Human Genetics

175

140

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Hereditary multiple exostoses (EXT; MIM 133700) is an autosomal dominant bone disorder characterized by the presence of multiple benign cartilage-capped tumors (exostoses). Besides suffering complications caused by the pressure of these exostoses on the surrounding tissues, EXT patients are at an increased risk for malignant chondrosarcoma, which may develop from an exostosis. EXT is genetically heterogeneous, and three loci have been identified so far: EXT1, on chromosome 8q23-q24; EXT2, on 11p11-p12; and EXT3, on the short arm of chromosome 19. The EXT1 and EXT2 genes were cloned recently, and they were shown to be homologous. We have now analyzed the EXT1 and EXT2 genes, in 26 EXT families originating from nine countries, to identify the underlying disease-causing mutation. Of the 26 families, 10 families had an EXT1 mutation, and 10 had an EXT2 mutation. Twelve of these mutations have never been described before. In addition, we have reviewed all EXT1 and EXT2 mutations reported so far, to determine the nature, frequency, and distribution of mutations that cause EXT. From this analysis, we conclude that mutations in either the EXT1 or the EXT2 gene are responsible for the majority of EXT cases. Most of the mutations in EXT1 and EXT2 cause premature termination of the EXT proteins, whereas missense mutations are rare. The development is thus mainly due to loss of function of the EXT genes, consistent with the hypothesis that the EXT genes have a tumor- suppressor function.

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“…Additional complications that cause symptoms include osseous deformity, fracture, vascular-nerve compression, neurologic sequelae, bursa formation, and malignant transformation [3,7]. Malignant transformation is seen in less than 1% to 2% of patients of solitary osteochondroma [2,9] and in 5%-25% of patients with multiple hereditary exostoses [1,2,10]. …”

Section: Discussionmentioning

confidence: 99%

A calcaneal osteochondroma with recurrence in a skeletally mature patient: a case report

Koplay

Toker

Şahin

et al. 2009

Cases J

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IntroductionOsteochondroma is the most common benign tumor of the skeleton. However, calcaneal osteochondroma is very rare. Osteochondromas grow during childhood through adolescence, but usually growing ends when the epiphyseal plates close. In an adult, growth of an osteochondroma suggests the diagnosis of malignant transformation to a chondrosarcoma. However, enlargement of an osteochondroma reported as benign after skeletal maturity is present in literature.Case presentationWe report the clinical and radiologic findings of a calcaneal osteochondroma with an extremely rare placement and painfull, rapid reccurence following surgical excision in a skeletally mature female. The lesion showed growth the first-operation later and was re-operated. Histopathological examination did not show malignancy.ConclusionIt should kept in mind that benign osteochondromas can show symptomatic growth in skeletally mature patients without malignant transformation.

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Hereditary multiple exostoses: Confirmation of linkage to chromosomes 8 and 11

Cited by 21 publications

References 13 publications

Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses

Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses

Mutations in the EXT1 and EXT2 Genes in Hereditary Multiple Exostoses

A calcaneal osteochondroma with recurrence in a skeletally mature patient: a case report

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