title: EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta.
abstract: Osteogenesis imperfecta (OI) comprises a group of inherited disorders characterized by bone fragility and increased susceptibility to fractures. Historically, the laboratory confirmation of the diagnosis OI rested on cultured dermal fibroblasts to identify decreased or abnormal production of abnormal type I (pro)collagen molecules, measured by gel electrophoresis. With the discovery of COL1A1 and COL1A2 gene variants as a cause of OI, sequence analysis of these genes was added to the diagnostic process. Nowadays, OI is known to be genetically heterogeneous. About 90% of individuals with OI are heterozygous for causative variants in the COL1A1 and COL1A2 genes. The majority of remaining affected individuals have recessively inherited forms of OI with the causative variants in the more recently discovered genes CRTAP, FKBP10, LEPRE1,PLOD2, PPIB, SERPINF1, SERPINH1 and SP7, or in other yet undiscovered genes. These advances in the molecular genetic diagnosis of OI prompted us to develop new guidelines for molecular testing and reporting of results in which we take into account that testing is also used to 'exclude' OI when there is suspicion of non-accidental injury. Diagnostic flow, methods and reporting scenarios were discussed during an international workshop with 17 clinicians and scientists from 11 countries and converged in these best practice guidelines for the laboratory diagnosis of OI.
authors.affiliation: Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands. fs.vandijk2@vumc.nl
authors.forename: Fleur S
authors.initials: FS
authors.lastname: van Dijk
authors.forename: Peter H
authors.initials: PH
authors.lastname: Byers
authors.forename: Raymond
authors.initials: R
authors.lastname: Dalgleish
authors.forename: Fransiska
authors.initials: F
authors.lastname: Malfait
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maugeri
authors.forename: Marianne
authors.initials: M
authors.lastname: Rohrbach
authors.forename: Sofie
authors.initials: S
authors.lastname: Symoens
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: Gerard
authors.initials: G
authors.lastname: Pals
mesh_terms: D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D005347:Fibroblasts / Q000166:cytology; D005817:Genetic Counseling / Q000592:standards; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000235:genetics; D005820:Genetic Testing / Q000379:methods / Q000592:standards*; D006579:Heterozygote; D006801:Humans; D040582:Inheritance Patterns; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000175:diagnosis* / Q000235:genetics; D019836:Preimplantation Diagnosis / Q000379:methods / Q000592:standards; D011296:Prenatal Diagnosis / Q000379:methods / Q000592:standards*
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain