Classification of Osteogenesis Imperfecta

Sillence, DavidO.; Dl, Rimoin

doi:10.1016/s0140-6736(78)90763-8

Cited by 156 publications

(96 citation statements)

References 5 publications

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“…An unknown proportion of very mild cases will most likely never come to medical attention. When the comprehensive studies by Sillence et al 14,31 were performed in the 1970s, molecular diagnostics was not available and the causative genes were not known. Later studies including molecular analysis are often skewed toward severe phenotypes, and cover only subsets of patients.…”

Section: Noteworthy Mutationsmentioning

confidence: 99%

Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

et al. 2015

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Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on 4100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1-and α2-chains were associated with the absence of dentinogenesis imperfecta (Po0.0001 vs 0.0049), while only those in the α1-chain were associated with blue sclera (P = 0.0110). Comparing glycine with serine substitutions, α1-alterations were associated with more severe phenotype (P = 0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (Po0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent 495% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in 495% of an entire OI population.

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Section: Noteworthy Mutationsmentioning

confidence: 99%

Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

et al. 2015

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“…Short stature, blue sclerae, laxity of ligaments, non-union of fractures, keloid and hyperplastic callus formation are among frequently encountered symptoms (1). The original clinical classification of OI defined four types on the basis of phenotypic severity (2,3). The clinical heterogeneity was reflected by a variety of mutations in the COL1A1 and COL1A2 genes that are thought to be the underlying cause of most cases of OI (4).…”

Section: Osteogenesis Imperfecta (Oi)mentioning

confidence: 99%

“…Following a 30-min incubation at 37°C, cells were plated onto plastic precoated with RGD-containing proteins at a density of 40,000 cells/cm 2 , and 36 h after plating, medium was aspirated and replaced with serum-free medium containing 50 Ci/ml [ 35 S]SO 4 2Ϫ . After 12 h of labeling, media were collected, and cell layers were either extracted using 4 M guanidinium HCl or dissolved in gel sample buffer (GSB, consisting of 30% glycerol, 4% SDS, 2 M urea in 0.625 M Tris-HCl buffer).…”

Section: Determination Of Structural Effects Of Different Matrix Growmentioning

confidence: 99%

Age-related Changes in Human Bone Proteoglycan Structure

Grzesik

Frazier

Shapiro

et al. 2002

Journal of Biological Chemistry

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Proteoglycans (PGs) are a family of molecules that undergo extensive post-translational modifications that include addition of glycosaminoglycan (GAG) chains as well as N-and O-linked oligosaccharides to the protein core. PG composition and structure have been reported to alter with age. To test whether the post-translational modifications to PGs can serve as in vitro surrogate end point markers for chronological age, the extent of GAG modifications was determined for PGs derived from normal human bone cells of 14 donors (age range, fetal to 60 years). Isolated cells were steady state radiolabeled with 35 SO 4 2؊ and [ 3 H]GlcN. For biglycan and decorin, iduronate content was linearly correlated with age (increased 1.5؋ between fetal and age 60 years). For the syndecan-like heparan sulfate PG, the N-sulfation of post-natal cells increased over 3.5-fold until reaching a plateau during the 4th decade of life. The amount of O-linked oligosaccharides was also found to decrease as a function of increasing normal donor age, whereas the specific activity of the metabolic precursor pool remained constant regardless of donor age. These age-related changes in post-translational modifications were then used to demonstrate that osteoblasts derived from patients with osteogenesis imperfecta did not exhibit facets of a pre-mature aging, but rather were arrested in a fetallike phenotypic state. A growth matrix rich in thrombospondin altered PG metabolism in osteoblastic cells, resulting in the production and secretion of the fetal-like (rich in O-linked oligosaccharides) forms of decorin and biglycan. This effect was qualitatively different from the effect of transforming growth factor-␤, which predominantly altered GAGs rather than O-linked oligosaccharides. No other Arg-Gly-Asp protein (fibronectin, vitronectin, type I collagen, osteopontin, and bone sialoprotein) showed any detectable effect on PG metabolism in bone cells. These results indicate that a proper matrix stoichiometry is critical for metabolism of PGs.

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“…Osteogenesis Imperfecta (OI) is a clinically and genotypically heterogeneous, heritable connective tissue disorder which results in fragile, deformed bones, short stature and low bone mass 1 . Most cases of OI are due to dominantly inherited mutations in COL1A1 or COL1A2 which affect the structure or quantity of type I collagen (Types I-IV) 2 3 .…”

Section: Introductionmentioning

confidence: 99%

Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect

Webb

Balasubramanian

Fratzl‐Zelman

et al. 2017

The Journal of Clinical Endocrinology &Amp; Metabolism

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ReuseUnless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. Disclosures: All authors state that they have no conflicts of interest. Takedown Supplemental data not included with this paper (see separate files)2 AbstractContext:Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI; OMIM 611236) by dysregulating intracellular calcium flux. Objectives:Clinical and bone material phenotype description and osteoblast differentiation studies. Design and Setting:Natural history study in paediatric research centres.Patients:Eight patients with type XIV OI. Main Outcome Measures:Clinical examinations included; bone mineral density, radiographs, echocardiography and muscle biopsy. Bone biopsy samples (n=3) were analysed for histomorphometry and bone mineral density distribution by quantitative backscattered electron microscopy and Raman microspectroscopy. Cellular differentiation studies were performed on proband osteoblasts and normal murine osteoclasts. Results:The clinical phenotype of type XIV OI ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband L1-L4 bone density Z-score was reduced (median -3.3 [range -4.77 to +0.1; n=7]), and increased by +1.7 (1.17 to 3.0; n=3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone mineralization density is normal/slightly increased. We demonstrate a complex osteoblast differentiation defect with decreased 3 expression of early markers and increased late, mineralisation-related markers.Predominance of TRIC-B over TRIC-A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover.Conclusions: OI type XIV has a bone histology, mineralization and osteoblast differentiation pattern that is distinct from type I OI. Probands are responsive to bisphosphonates but show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities.4

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Classification of Osteogenesis Imperfecta

Cited by 156 publications

References 5 publications

Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

Age-related Changes in Human Bone Proteoglycan Structure

Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect

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