Achondrogenesis within the scope of connately manifested generalized skeletal dysplasias

Wiedemann, H. R.; Remagen, Wolfgang; Hienz, H. A.; Gorlin, Robert J.; Maroteaux, P

doi:10.1007/bf00436949

Cited by 21 publications

(5 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contradistinction to the cells, the matrix was basically unchanged and present in adequate amounts, a finding in agreement with that of Yang [19]. Our material does not permit conclusions on the calcifiability of the matrix, which has been reported as being absent in achondrogenesis [15]--a finding of particular interest in view of the unexplained pathogenesis of the disorder. The presence of both ground substance and collagen fibrils indicates a previously undisturbed function of the chondrocytes.…”

Section: Discussionsupporting

confidence: 85%

Achondrogenesis type I: Light and electron-microscopic studies

Molz

Spycher

1980

Eur J Pediatr

View full text Add to dashboard Cite

The light- and electron-microscopic structure of articular and costal cartilage in a case of achondrogenesis type I has been described. The most characteristic ultrastructural change in the chondrocytes was conspicuous dilatation of the rough endoplasmatic reticulum (RER) which contained amorphous electronopaque material. This change in the RER was accompanied by marked hypertrophy of the Golgi apparatus; the matrix was basically unchanged.

show abstract

Section: Discussionsupporting

confidence: 85%

Achondrogenesis type I: Light and electron-microscopic studies

Molz

Spycher

1980

Eur J Pediatr

View full text Add to dashboard Cite

show abstract

“…It remains our view that until the precise biochemical defects have been elucidated, no definitive classification is possible. This is also the view expressed by Wiedemann et al (1974) whose collection of 6 cases is still the largest reported. The difficulties in attempting a classification based on 2 cases plus a review of previous studies are exemplified by the necessity for a 'readjustment of eponyms ' which Yang et al (1975) subsequently reported.…”

supporting

confidence: 59%

Achondrogenesis type I.

Yang¹,

Bernstein²

1977

Archives of Disease in Childhood

View full text Add to dashboard Cite

“…The cell extract was clarified by centrifugation at 12,100 ϫ g for 15 min and the protein content was estimated (BCA Protein Assay, Pierce) using bovine serum albumin as standard. A reaction mixture of 55 l containing 5 l of 0.1 M ATP, 2 l of 10 mM cysteine-HCl, 6 Ci of carrier-free Na 2 …”

Section: Methodsmentioning

confidence: 99%

“…Achondrogenesis type 1B (ACG-1B) 1 (1) is an autosomal recessive, lethal chondrodysplasia with severe underdevelopment of the skeleton, extreme micromelia, and death before or immediately after birth because of thoracic hypoplasia (1)(2)(3)(4)(5)(6)(7)(8). Both radiological and histological features differentiate ACG-1B from achondrogenesis type 1A and achondrogenesis type 2 (3).…”

Section: S]sulfate Relative To [mentioning

confidence: 99%

Undersulfation of Proteoglycans Synthesized by Chondrocytes from a Patient with Achondrogenesis Type 1B Homozygous for an L483P Substitution in the Diastrophic Dysplasia Sulfate Transporter

Rossi

Bonaventure

Delezoide

et al. 1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

). To ascertain the consequences of the sulfate transport defect on proteoglycan synthesis, we studied the structure and sulfation of proteoglycans in cartilage tissue and in fibroblast and chondrocyte cultures from a fetus with achondrogenesis 1B. Proteoglycans extracted from epiphyseal cartilage and separated on agarose gels migrated more slowly than controls and stained poorly with alcian blue. The patient's cultured cells showed reduced incorporation of [ S]sulfate relative to [3 H]glucosamine, impaired uptake of sulfate, and higher resistance to chromate toxicity compared to control cells. Epiphyseal chondrocytes cultured in alginate beads synthesized proteoglycans of normal molecular size as judged by gel filtration chromatography, but undersulfated as judged by ion exchange chromatography and by the amount of nonsulfated disaccharide. High performance liquid chromatography analysis of chondroitinase-digested proteoglycans showed that sulfated disaccharides were present, although in reduced amounts, indicating that at least in vitro, other sources of sulfate can partially compensate for sulfate deficiency. A t1475c transition causing a L483P substitution in the eleventh transmembrane domain of the sulfate/chloride antiporter was present on both alleles in the patient who was the product of a consanguineous marriage. The results indicate that the defect of sulfate transport is expressed in both chondrocytes and fibroblasts and results in the synthesis of proteoglycans bearing glycosaminoglycan chains which are poorly sulfated but of normal length.Achondrogenesis type 1B (ACG-1B) 1 (1) is an autosomal recessive, lethal chondrodysplasia with severe underdevelopment of the skeleton, extreme micromelia, and death before or immediately after birth because of thoracic hypoplasia (1-8). Both radiological and histological features differentiate ACG-1B from achondrogenesis type 1A and achondrogenesis type 2 (3). In ACG-1B, cartilage matrix contains abnormally coarse collagen fibers and stains poorly with cationic dyes which have affinity for sulfated proteoglycans (toluidine blue or alcian blue) (4,8). Evidence of undersulfation of proteoglycans (PGs) in cartilage on the basis of histological findings and in fibroblast cultures, together with the demonstration of insufficient formation of activated sulfate metabolites, was obtained recently in one patient with ACG-1B (8). Further studies have revealed that ACG-1B is caused not by a defect in the metabolic activation of sulfate, as originally concluded (8), but by a sulfate uptake defect caused by mutations in the sulfate transporter gene (9) originally isolated as the locus responsible for the non-lethal disorder, diastrophic dysplasia (10). The pathogenesis of the severe developmental defect of the skeleton seen in ACG-1B is believed to involve undersulfation of cartilage PGs, as suggested by both the staining properties of cartilage and its markedly reduced sulfate content (9), but direct demonstration of undersulfation of individual cartilage PGs is lacking. We h...

show abstract

Achondrogenesis within the scope of connately manifested generalized skeletal dysplasias

Cited by 21 publications

References 33 publications

Achondrogenesis type I: Light and electron-microscopic studies

Achondrogenesis type I: Light and electron-microscopic studies

Achondrogenesis type I.

Undersulfation of Proteoglycans Synthesized by Chondrocytes from a Patient with Achondrogenesis Type 1B Homozygous for an L483P Substitution in the Diastrophic Dysplasia Sulfate Transporter

Contact Info

Product

Resources

About