title: Molecular diagnosis in children with fractures but no extraskeletal signs of osteogenesis imperfecta.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Shriners Hospital for Children and McGill University, 1003 Decarie, Montreal, Québec, H4A 0A9, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Bardai
authors.affiliation: Children's Hospital of Eastern Ontario, Ontario, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Ward
authors.affiliation: Shriners Hospital for Children and McGill University, 1003 Decarie, Montreal, Québec, H4A 0A9, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Trejo
authors.affiliation: Shriners Hospital for Children and McGill University, 1003 Decarie, Montreal, Québec, H4A 0A9, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Moffatt
authors.affiliation: Shriners Hospital for Children and McGill University, 1003 Decarie, Montreal, Québec, H4A 0A9, Canada.
authors.forename: F H
authors.initials: FH
authors.lastname: Glorieux
authors.affiliation: Shriners Hospital for Children and McGill University, 1003 Decarie, Montreal, Québec, H4A 0A9, Canada. frauch@shriners.mcgill.ca.
authors.forename: F
authors.initials: F
authors.lastname: Rauch
mesh_terms: D000293:Adolescent; D015519:Bone Density / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D005598:Fractures, Spontaneous / Q000209:etiology* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000150:complications / Q000175:diagnosis* / Q000235:genetics
chemical_list: C000601279:COL1A2 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5
keywords: Children; Fractures; Mutations; Next-generation sequencing; Osteogenesis imperfecta