Achondrogenesis type I: Delineation of further heterogeneity and identification of two distinct subgroups

Borochowitz, Z.; Lachman, Ralph S.; Adomian, G.; Spear, Gerald S.; Jones, Kenneth Lyons; Rimoin, David L.

doi:10.1016/s0022-3476(88)80113-6

Cited by 68 publications

(34 citation statements)

References 25 publications

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“…ACG type 1A (ACG-1A) with apparently normal cartilage matrix but inclusions in chondrocytes, ACG type 1B (ACG-1B) with abnormal cartilage matrix. 4 These findings were confirmed by another group shortly thereafter. 5 Some cases have been published previously and diagnosed as ACG-1B, and the other cases was diagnosed as ACG-1A, while Parenti case this may be classified as ACG type 2 (ACG-2).…”

Section: Introductionmentioning

confidence: 64%

The genetic aspect and morphological appearance of achondrogenesis

Parwanto

2017

Int J Reprod Contracept Obstet Gynecol

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Achondrogenesis (ACG) is a number of disorders that are the most severe form of congenital chondrodysplasia characterized with bones and cartilage malformation. Generally, characteristic of ACG is a small body, short limbs, and other skeletal abnormalities. As a result of infants with ACG their serious health problems, usually born prematurely, are stillborn, or die shortly after birth from respiratory failure. Currently 3 type variants of ACG such as ACG-1A, ACG-1B and ACG-2. ACG-1A appears to be autosomal recessive (AR), with thyroid hormone receptor interactor 11 (TRIP11) gen mutation, while ACG1B also appears to be AR, with diastrophic dysplasia sulfate transporter or DTDST (SLC26A2) gen mutation. ACG-2 is caused by autosomal dominant (AD), with type 2 collagen (COL2A1) gen mutation. ACG-1A had characterizid such as physis abnormal, vertebral bodies with unossified or smal and oval, skull poorly ossified, periodic acid–Schiff (PAS) stain positive chondrocyte inclusions finding in long bones. ACG-1B had physis abnormal, vertebral bodies with unossified or smal and oval, skull ossified, perichondrocyte collagen rings finding in long bones. ACG-2 also had physis abnormal, metaphyseal cupping, vertebral bodies with unossified or small and oval, enlarged chondrocyte lacunae.

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Section: Introductionmentioning

confidence: 64%

The genetic aspect and morphological appearance of achondrogenesis

Parwanto

2017

Int J Reprod Contracept Obstet Gynecol

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“…These diseases are caused by mutations in the collagen type II gene [Korkko et al, 2000]. Types IA and B achondrogenesis are more severe and transmission is autosomal recessive [Borochowitz et al, 1988;Rossi and Superti-Furga, 2001]. In thanatophoric dysplasia, the vertebral bodies are reduced with a cupped aspect of the phalanges, but some of the defects specific to that disease were not present in the patients reported here (i.e., very short limbs, short thick ribs, H-, U-, or reversed U-shape vertebrae).…”

Section: Discussionmentioning

confidence: 99%

X-linked dominant chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia

Chassaing

Siani²,

Carles

et al. 2005

Am. J. Med. Genet.

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We describe a family with an X-linked dominant chondrodysplasia. Four males and six females were affected through four generations. Identification of skeletal abnormalities and hydrocephaly during the pregnancy of three male fetuses led to termination of the pregnancies. A fourth affected male died at 6 days of life. The four patients had chondrodysplasia, hydrocephaly, and facial features with microphthalmia. Radiographs showed severe platyspondyly and various bone abnormalities including a distinctive metaphyseal cupping of the metacarpals, metatarsals, and phalanges. The affected females were less affected and showed small stature, sometimes associated with body asymmetry and mild mental retardation. This condition appears to be a previously unrecognized X-linked dominant chondrodysplasia.

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“…Histologic analysis of cartilage showed typical collagenous rings surrounding chondrocytes asso-ciated with reduced ground substance and coarse collagen fibrils which allowed diagnosis of achondrogenesis type 1B rather than type 1A (Fig. 1B) (3,4,7,8).…”

Section: Methodsmentioning

confidence: 99%

“…Finally, in the patient's cell-associated matrix (0.2 and 4 M GdmCl fraction), an 3 H-labeled peak free of 35 S (fractions 37-43) and eluting in the void volume of the column (V 0 ) was present (Fig. 4, E and G).…”

Section: S/mentioning

confidence: 96%

“…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%

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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

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). 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...

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Achondrogenesis type I: Delineation of further heterogeneity and identification of two distinct subgroups

Cited by 68 publications

References 25 publications

The genetic aspect and morphological appearance of achondrogenesis

The genetic aspect and morphological appearance of achondrogenesis

X-linked dominant chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia

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

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