Osteogenesis imperfecta type III with intracranial hemorrhage and brachydactyly associated with mutations in exon 49 of COL1A2

Faqeih, Eissa; Roughley, Peter J.; Glorieux, Francis H.; Rauch, Frank

doi:10.1002/ajmg.a.32653

Cited by 22 publications

(21 citation statements)

References 15 publications

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“…9 The other mutations included in this report have been entered into a database of OI mutations (http://www.le.ac.uk/ge/collagen/). 3,4 Mutations for which there was no prior entry in this database were labeled as 'novel.…”

Section: Collagen Type I Mutation Analysismentioning

confidence: 99%

Genotype–phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I

et al. 2010

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Osteogenesis imperfecta (OI) is a heritable disorder with bone fragility that is often associated with short stature, tooth abnormalities (dentinogenesis imperfecta), and blue sclera. The most common mutations associated with OI result from the substitution for glycine by another amino acid in the triple helical domain of either the a1 or the a2 chain of collagen type I. In this study, we compared the results of genotype analysis and clinical examination in 161 OI patients (median age: 13 years) who had glycine mutations in the triple helical domain of a1(I) (n¼67) or a2(I) (n¼94). Serine substitutions were the most frequently encountered type of mutation in both chains. Compared with patients with serine substitutions in a2(I) (n¼40), patients with serine substitutions in a1(I) (n¼42) on average were shorter (median height z-score À6.0 vs À3.4; P¼0.005), indicating that a1(I) mutations cause a more severe phenotype. Height correlated with the location of the mutation in the a2(I) chain but not in the a1(I) chain. Patients with mutations affecting the first 120 amino acids at the amino-terminal end of the collagen type I triple helix had blue sclera but did not have dentinogenesis imperfecta. Among patients from different families sharing the same mutation, about 90 and 75% were concordant for dentinogenesis imperfecta and blue sclera, respectively. These data should be useful to predict disease phenotype in newly diagnosed OI patients.

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Section: Collagen Type I Mutation Analysismentioning

confidence: 99%

Genotype–phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I

et al. 2010

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“…These findings reflect the substitution of a glycine near the carboxyl-terminal end of the triple-helical domain by a larger amino acid and the slow folding and increased posttranslational modification of the unwound chains. The sample from the patient with moderate OI (type IV) has a much more subtle defect in chain mobility, represented by the blurring of the space between the proa1(I) and proa1(III) chains, and illustrates one of the aspects of the ''art'' of interpreting protein studies result in a relatively high bone mass with skeletal fragility [11], and substitutions for glycine near the very end of the triple-helical domain of proa2(I) encoded in exon 49 of the COL1A2 gene have been associated with brachydactyly and intracerebral hemorrhage, in addition to a severe OI phenotype [12].…”

Section: Dominantly Inherited Oimentioning

confidence: 99%

Recent Advances in Osteogenesis Imperfecta

Cundy

2012

Calcif Tissue Int

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"Osteogenesis imperfecta" is a term used to describe a group of genetic disorders of variable phenotype usually defined by recurrent fractures, low bone mass, and skeletal fragility. Most cases are associated with mutations in one of the type I collagen genes, but in recent years several other forms have been identified with recessive inheritance. In most instances the latter result from mutations in genes encoding proteins involved in type I collagen's complex posttranslational modification or in genes regulating bone matrix homeostasis. This article reviews the recent discoveries and an approach to classification and diagnosis. Bisphosphonates are widely used in patients with osteogenesis imperfecta, but some important questions about their optimal usage, their utility in children and adults with milder phenotypes, and their potential adverse effects are not yet resolved.

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“…For example, finding the OI type V specific IFITM5 mutation indicates that the patient has a high risk of developing hyperplastic callus, radial head dislocation, and abnormalities in the cranio–cervical junction . Mutations affecting the C‐propeptide of the collagen type I alpha 1 chain are frequently associated with hip dysplasia, and glycine substitutions caused by mutations in exon 49 of COL1A2 may predispose to intracranial hemorrhage …”

Section: Genetic Testing For Osteogenesis Imperfectamentioning

confidence: 99%

Osteogenesis Imperfecta: New Perspectives From Clinical and Translational Research

2019

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Osteogenesis imperfecta (OI) is a monogenic bone fragility disorder that usually is caused by mutations in one of the two genes coding for collagen type I alpha chains, COL1A1 or COL1A2 . Mutations in at least 18 other genes can also lead to an OI phenotype. As genetic testing is more widely used, mutations in these genes are also more frequently discovered in individuals who have a propensity for fractures, but who do not have other typical clinical characteristics of OI. Intravenous bisphosphonate therapy is still the most widely used drug treatment approach. Preclinical studies in OI mouse models have shown encouraging effects when the antiresorptive effect of a bisphosphonate was combined with bone anabolic therapy using a sclerostin antibody. Other novel experimental treatment approaches include inhibition of transforming growth factor beta signaling with a neutralizing antibody and the inhibition of myostatin and activin A by a soluble activin receptor 2B. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

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Osteogenesis imperfecta type III with intracranial hemorrhage and brachydactyly associated with mutations in exon 49 of COL1A2

Cited by 22 publications

References 15 publications

Genotype–phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I

Genotype–phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I

Recent Advances in Osteogenesis Imperfecta

Osteogenesis Imperfecta: New Perspectives From Clinical and Translational Research

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