Evidence map›Paper›PMID 34091789›Full record

Observational studyArchives of osteoporosis2021

Diagnostic utility of next-generation sequence genetic panel testing in children presenting with a clinically significant fracture history.

Jennifer Harrington, Abdulmajeed AlSubaihin, Lucie Dupuis, Peter Kannu, Roberto Mendoza-Londono, Andrew Howard

Abstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in Archives of osteoporosis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Role of Notch signaling in corticalization.Journal of endocrinological investigation · 2026
    Review
  2. Article
  3. Review
  4. Update on the Genetics of Osteogenesis Imperfecta.Calcified tissue international · 2024
    Review
  5. Advances in Diagnosis and Management of Childhood OsteoporosisJournal of clinical research in pediatric endocrinology · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Jennifer HarringtonDivision of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada. jenny.harrington@sa.gov.au.
Abdulmajeed AlSubaihinDepartment of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Lucie DupuisDivision of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Peter KannuDivision of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Roberto Mendoza-LondonoDivision of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Andrew HowardDivision of Orthopedics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Hospital for Sick Children · CAKing Saud University · SASickKids Foundation · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We assessed the diagnostic utility of genetic panel testing to detect pathogenic variants associated with osteogenesis imperfecta in children presenting with multiple fractures. Thirty-five percent of children had a pathogenic variant. A history of a femur fracture or a first fracture occurring under 2 years of age were significant clinical predictors. PURPOSE: The use of next-generation sequencing (NGS) genetic panels offers a comprehensive rapid diagnostic test to evaluate for pathogenic variants in the expanding list of genes associated with osteogenesis imperfecta (OI). We aimed to assess the diagnostic utility of this method in children with a clinically significant fracture history.

methodsNGS panel testing was performed in 87 children presenting with multiple long bone or vertebral fractures. Subjects with a known family history of OI were excluded. Associations between genetic findings and clinical characteristics were analyzed in a retrospective observational study.

resultsThirty-five percent of patients were found to have a disease-causing variant, with a higher detection rate in those patients with extra-skeletal features of OI (94 vs. 20%, p < 0.001). In subjects with extra-skeletal clinical OI features, 69% were found to have pathogenic variants in COL1A1 or COL1A2. In children without extra-skeletal features, 14 of 70 (20%) had pathogenic variants, of which 7 were variants in type 1 collagen, and the remaining 7 variants were associated with osteoblast function or signaling (PLS3, SP7, LRP5). Clinical predictors for detecting a disease-causing variant included a history of having a first fracture that occurred under 2 years of age (Odds ratio 5.5, 95%CI 1.8, 16.9) and a history of a femur fracture (Odds ratio 3.3, 95%CI 1.0, 11.1).

conclusionNGS panel testing will detect causative pathogenic variants in up to a third of children with a clinically significant fracture history, particularly where there is a history of early femur fracture.

Indexed as

Fractures, BoneOsteogenesis ImperfectaBone and BonesChildCollagen Type IHumansRetrospective StudiesCollagen Type IChildrenFracturesGenetic testingOsteogenesis imperfecta

Identifiers

PMID34091789
OpenAlexW3168122188

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.