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Osteoporosis International

, Volume 28, Issue 7, pp 2095–2101 | Cite as

Molecular diagnosis in children with fractures but no extraskeletal signs of osteogenesis imperfecta

  • G. Bardai
  • L. M. Ward
  • P. Trejo
  • P. Moffatt
  • F. H. Glorieux
  • F. RauchEmail author
Original Article

Abstract

Summary

In 26 of 94 individuals (28%) below 21 years of age who had a significant fracture history but did not have extraskeletal features of osteogenesis imperfecta (OI), we detected disease-causing mutations in OI-associated genes.

Introduction

In children who have mild bone fragility but do not have extraskeletal features of OI, it can be difficult to establish a diagnosis on clinical grounds. Here, we assessed the diagnostic yield of genetic testing in this context, by sequencing a panel of genes that are associated with OI.

Methods

DNA sequence analysis was performed on 94 individuals below 21 years of age who had a significant fracture history but had white sclera and no signs of dentinogenesis imperfecta.

Results

Disease-causing variants were detected in 28% of individuals and affected 5 different genes. Twelve individuals had mutations in COL1A1 or COL1A2, 8 in LRP5, 4 in BMP1, and 2 in PLS3.

Conclusions

DNA sequence analysis of currently known OI-associated genes identified disease-causing variants in more than a quarter of individuals with a significant fracture history but without extraskeletal manifestations of OI.

Keywords

Children Fractures Mutations Next-generation sequencing Osteogenesis imperfecta 

Notes

Acknowledgments

FR received salary support from the Chercheur-Boursier Clinicien program of the Fonds de Recherche du Québec—Santé. LMW is supported by the Research Chair program at the University of Ottawa and the Departments of Pediatrics and Surgery, Children’s Hospital of Eastern Ontario. This study was supported by the Shriners of North America.

Web resources

Exome Aggregation Consortium (ExAC) Browser: http://exac.broadinstitute.org/.

Online Mendelian Inheritance in Man (OMIM), http://www.omim.org

Osteogenesis Imperfecta Variant Database: https://oi.gene.le.ac.uk/

UCSC database, version hg19: http://www.genome.ucsc.edu/

Authors’ contributions

GB performed analyses; LMW, PT and FHG contributed patient information; PM and FHG reviewed sequencing data; and FR conceptualized the project, contributed patient information, finalized the report, and accepts responsibility for the integrity of the data analysis. All authors have read and approved of the final version of the manuscript.

Compliance with ethical standards

Ethics statement

The study was approved by the Institutional Review Board of McGill University and the Research Ethics Board at the Children’s Hospital of Eastern Ontario.

Conflicts of interest

None.

Supplementary material

198_2017_4031_MOESM1_ESM.docx (63 kb)
ESM 1 (DOCX 63 kb).

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2017

Authors and Affiliations

  • G. Bardai
    • 1
  • L. M. Ward
    • 2
  • P. Trejo
    • 1
  • P. Moffatt
    • 1
  • F. H. Glorieux
    • 1
  • F. Rauch
    • 1
    Email author
  1. 1.Shriners Hospital for Children and McGill UniversityMontrealCanada
  2. 2.Children’s Hospital of Eastern OntarioOntarioCanada

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