A 4-Megabase YAC Contig That Spans the Langer-Giedion Syndrome Region on Human Chromosome 8q24.1: Use in Refining the Location of the Trichorhinophalangeal Syndrome and Multiple Exostoses Genes (TRPS1 and EXT1)

Hou, Jiakai; Parrish, Julia E.; Lüdecke, Hermann‐Josef; Sapru, M.; Wang, Y.; Chen, Wen Shan; Hill, Andrew P.; Siegel‐Bartelt, J.; Northrup, Hope; Elder, F.F.B.; Chinault, Craig; Horsthemke, Bernhard; Wagner, Michael J.; Wells, Dan E.

doi:10.1006/geno.1995.1218

Cited by 62 publications

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“…Cytogenetic and molecular studies have defined the critical region for Langer-Giedion syndrome as 8q24.1 [Bü hler and Malik, 1984;Hou et al, 1995;Parrish et al, 1991]. Langer-Giedion syndrome (TRPS II) is thought to be a contiguous gene syndrome and includes the phenotypes of trichorhino-phalangeal syndrome, type I (TRPS I) and multiple cartilaginous exostoses (EXT I).…”

Section: Discussionmentioning

confidence: 99%

Tibial hemimelia in Langer-Giedion syndrome?possible gene location for tibial hemimelia at 8q

Stevens

Moore

1999

Am. J. Med. Genet.

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We report on a girl with Langer-Giedion syndrome or tricho-rhino-phalangeal syndrome, type II (TRPS II) with deletion on 8q, and the unusual findings of bilateral tibial hemimelia and unilateral absence of the ulna. An 8-year-old boy with TRPS II with bilateral tibial hemimelia was reported by Turleau et al. [1982: Hum. Genet. 62:183-187]. The critical region for TRPS II is 8q24.1. Although no genes involving limb development in the human have been identified in this region, two mouse syndromes are localized to the homologous chromosome region of 9A1-A4 which involve limb abnormalities. We propose that a gene involved in limb development is contiguous with the TRPS II gene which, when deleted, may cause tibial hemimelia.

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Section: Discussionmentioning

confidence: 99%

Tibial hemimelia in Langer-Giedion syndrome?possible gene location for tibial hemimelia at 8q

Stevens

Moore

1999

Am. J. Med. Genet.

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“…The TRPS1 gene appears to encode a zinc-finger transcription factor, which is located proximal to the EXT1 tumor suppressor gene. The contiguous gene syndrome whose deletions encompass both the EXT1 and TRPS1 genes is called Langer-Giedion syndrome (LGS) or TRPS II (Hou et al 1995;Lüdecke et al 1995). TRPS II shares the characteristic features of TRPS I with the addition of multiple exostoses, whereas TRPS III only differs clinically from TRPS I by the appearance of severe brachydactyly and extreme shortness of stature (Niikawa and Kamei 1986).…”

Section: Introductionmentioning

confidence: 99%

Analysis of novel and recurrent mutations responsible for the tricho-rhino-phalangeal syndromes

et al. 2002

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The tricho-rhino-phalangeal syndromes (TRPS type I, II, and III) are autosomal dominant disorders sharing the following characteristics: slowly growing and sparse scalp hair, medially thick and laterally thin eyebrows, bulbous tip of the nose, long flat philtrum, thin upper lip with vermilion border, and protruding ears. In addition, individuals with TRPS generally share skeletal and bone anomalies, including shortening of the phalanges and metacarpals (mild to severe brachydactyly), cone-shaped epiphyses, hip dysplasia, and short stature. The etiology of the different types of TRPS can result from either single base pair mutations, or the complete deletion of the TRPS1 gene, which encodes a zinc-finger transcription factor located on chromosomal band 8q24.1. We have identified nine heterozygous mutations, five novel and four recurrent, in unrelated families diagnosed with TRPS. The five novel mutations identified show 1-or 2-bp deletions and a single base substitution, whereas all of the recurrent mutations are single base substitutions. Seven of the nine mutations result in a premature stop codon, leading to a truncated, nonfunctional TRPS1 protein. The final two mutations are missense mutations in the GATA DNA binding zinc finger, which is believed to be important for the protein's normal function.

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“…This region of linkage group 19 is syntenic to the human chromosome 8 region. Human syndecan-2 maps to 8q23.2, 50 human TRPS1 gene maps to 8q24.12, [33][34][35] and human EXT1 maps to 8q24.11-q24.13. 36 Thus, human syndecan-2 is likely to be the true orthologue of zebrafish syndecan-2.…”

Section: Zebrafish Syndecan-2 Is Orthologous To Human and Mouse Syndementioning

confidence: 99%

“…Radiation hybrid mapping placed zebrafish syndecan-2 in the linkage group 19, closely linked to marker Z13292 (distance 16.49 cR, LOD score of 11.3), which is located closest to the TRPS1 gene and the EXT1 gene. This region of linkage group 19 is syntenic to the human chromosome 8 region.Human syndecan-2 maps to 8q23.2, 50 human TRPS1 gene maps to 8q24.12, [33][34][35] and human EXT1 maps to 8q24.11-q24.13. 36 Thus, human syndecan-2 is likely to be the true orthologue of zebrafish syndecan-2.…”

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confidence: 99%

Syndecan-2 is essential for angiogenic sprouting during zebrafish development

Chen

Hermanson

Ekker

2004

Blood

138

101

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We used a morpholino-based gene-targeting screen to identify a novel protein essential for vascular development using the zebrafish, Danio rerio. We show that syndecan-2, a cell-surface heparan sulfate proteoglycan, is essential for angiogenic sprouting during embryogenesis. The vascular function of syndecan-2 is likely conserved, as zebrafish and mouse syndecan-2 show similar expression patterns around major trunk vessels, and human syndecan-2 can restore angiogenic sprouting in syndecan-2 morphants. In contrast, forced expression of a truncated form of syndecan-2 results in embryos with defects in angiogenesis, indicating that the highly conserved cytoplasmic tail is important for the vascular function of syndecan-2. We further show that vascular endothelial growth factor (VEGF) and syndecan-2 genetically interact in vivo using both gain-of-function and loss-offunction studies in zebrafish. VEGF-mediated ectopic signaling is compromised in syndecan-2 morphants, and ectopic syndecan-2 potentiates ectopic VEGF signaling. Syndecan-2 as a novel angiogenic factor is a potential candidate for use in the development of angiogenesis-based therapies. IntroductionVascular formation is composed of 2 processes, vasculogenesis and angiogenesis. In vasculogenesis, angioblasts derived from the lateral mesoderm migrate and differentiate into endothelial cells that form the tubular structures of primary vasculature. In angiogenesis, new vessels sprout from pre-existing vasculature and are further remodeled to form mature blood vessels. Angiogenesis is an important process during development, various physiologic phenomena, and pathologic conditions such as tumor growth and diabetic retinopathy. 1 Growth factors such as vascular endothelial growth factor (VEGF), angiopoietins, and ephrins play key roles during angiogenesis. [1][2][3] Identification and characterization of novel angiogenic factors during vertebrate development may further the understanding of key molecular players in angiogenesis as well as hold promise for potential application in angiogenesis-based therapies. [4][5][6] Conservation of vascular development in vertebrates 7 and the capacity to effectively target this process using morpholinos 8 allowed us to embark on a morpholino-based screen for novel angiogenic factors using zebrafish as the model system. Morpholinos were designed based on 5Ј leader sequences from a collection of zebrafish expressed sequence tags (ESTs) with high homology to human, Drosophila, or Fugu gene. Bioinformatics methods to enrich for partial sequences of cell-surface or secreted proteins based on full-length reference protein data sets have been determined as previously described. 9 As part of this ongoing effort, we have identified syndecan-2 (syn-2), a cell-surface heparan sulfate proteoglycan, as a novel factor essential for angiogenic sprouting during vascular development.Previous studies have demonstrated the important roles played by heparan sulfate proteoglycans (HSPGs) in a variety of biologic processes such as early embryon...

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A 4-Megabase YAC Contig That Spans the Langer-Giedion Syndrome Region on Human Chromosome 8q24.1: Use in Refining the Location of the Trichorhinophalangeal Syndrome and Multiple Exostoses Genes (TRPS1 and EXT1)

Cited by 62 publications

References 0 publications

Tibial hemimelia in Langer-Giedion syndrome?possible gene location for tibial hemimelia at 8q

Tibial hemimelia in Langer-Giedion syndrome?possible gene location for tibial hemimelia at 8q

Analysis of novel and recurrent mutations responsible for the tricho-rhino-phalangeal syndromes

Syndecan-2 is essential for angiogenic sprouting during zebrafish development

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