Identification and Characterization of a Novel Member of the EXT Gene Family, EXTL2

Wuyts, Wim; Hul, Wim Van; Hendrickx, Jan; Speleman, Frank; Wauters, J.; Boulle, Kristel De; Roy, Nadine Van; Agtmael, Tom Van; Bossuyt, P.; Willems, Patrick J.

doi:10.1159/000484796

Cited by 87 publications

(41 citation statements)

References 21 publications

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“…EXTL2 is an alpha-1, 4-Nacetylhexosaminyltransferase involved in the biosynthesis of heparin/heparan sulfate and is a member of the hereditary multiple exostoses gene family of tumour suppressors. [43][44][45] Mutations in two other members of this gene family, EXT1 and EXT2, have been shown to cause hereditary multiple exostosis (HME) syndrome types I (EXT1; MIM 133700) and II (EXT2; MIM 133701). Approximately 50% of patients with HME show short stature, linking this gene to abnormal growth.…”

Section: Discussionmentioning

confidence: 99%

A male-specific quantitative trait locus on 1p21 controlling human stature

Sammalisto

Hiekkalinna²,

Suviolahti³

et al. 2005

Journal of Medical Genetics

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Background: Many genome-wide scans aimed at complex traits have been statistically underpowered due to small sample size. Combining data from several genome-wide screens with comparable quantitative phenotype data should improve statistical power for the localisation of genomic regions contributing to these traits. Objective: To perform a genome-wide screen for loci affecting adult stature by combined analysis of four previously performed genome-wide scans. Methods: We developed a web based computer tool, Cartographer, for combining genetic marker maps which positions genetic markers accurately using the July 2003 release of the human genome sequence and the deCODE genetic map. Using Cartographer, we combined the primary genotype data from four genome-wide scans and performed variance components (VC) linkage analyses for human stature on the pooled dataset of 1417 individuals from 277 families and performed VC analyses for males and females separately. Results: We found significant linkage to stature on 1p21 (multipoint LOD score 4.25) and suggestive linkages on 9p24 and 18q21 (multipoint LOD scores 2.57 and 2.39, respectively) in males-only analyses. We also found suggestive linkage to 4q35 and 22q13 (multipoint LOD scores 2.18 and 2.85, respectively) when we analysed both females and males and to 13q12 (multipoint LOD score 2.66) in females-only analyses. Conclusions: We strengthened the evidence for linkage to previously reported quantitative trait loci (QTL) for stature and also found significant evidence of a novel male-specific QTL on 1p21. Further investigation of several interesting candidate genes in this region will help towards characterisation of this first sexspecific locus affecting human stature.

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Section: Discussionmentioning

confidence: 99%

A male-specific quantitative trait locus on 1p21 controlling human stature

Sammalisto

Hiekkalinna²,

Suviolahti³

et al. 2005

Journal of Medical Genetics

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“…EXTL1 , EXTL2 and EXTL3 are located at 1p36.1 [40], 1p11-p12 [41] and 8p12-p22 [42], respectively. No linkage with Multiple Osteochondromas or other bone diseases has been documented for these genes [43].…”

Section: Geneticsmentioning

confidence: 99%

Multiple Osteochondromas: Clinicopathological and Genetic Spectrum and Suggestions for Clinical Management

Hameetman

Bovée

Taminiau

et al. 2004

Hered Cancer Clin Pract

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Multiple Osteochondromas is an autosomal dominant disorder characterised by the presence of multiple osteochondromas and a variety of orthopaedic deformities. Two genes causative of Multiple Osteochondromas, Exostosin-1 (EXT1) and Exostosin-2 (EXT2), have been identified, which act as tumour suppressor genes. Osteochondroma can progress towards its malignant counterpart, secondary peripheral chondrosarcoma and therefore adequate follow-up of Multiple Osteochondroma patients is important in order to detect malignant transformation early.This review summarizes the considerable recent basic scientific and clinical understanding resulting in a multi-step genetic model for peripheral cartilaginous tumorigenesis. This enabled us to suggest guidelines for clinical management of Multiple Osteochondroma patients. When a patient is suspected to have Multiple Osteochondroma, the radiologic documentation, histology and patient history have to be carefully reviewed, preferably by experts and if indicated for Multiple Osteochondromas, peripheral blood of the patient can be screened for germline mutations in either EXT1 or EXT2. After the Multiple Osteochondroma diagnosis is established and all tumours are identified, a regular follow-up including plain radiographs and base-line bone scan are recommended.

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“…Four have been identified so far: EXTL, EXTL2, EXTL3, and EXTL2P, localized to chromosome regions 1p36.1, 1p11-12, 8p12-22, and 2q24-31, respectively. [48][49][50] None has yet been shown to be responsible for the remaining 20 per cent of individuals with hereditary multiple exostoses who fail to exhibit germline mutations in EXT1 or EXT2 genes.…”

Section: A Neoplastic Pathogenesis For Osteochondromas-genetic Evidencementioning

confidence: 99%