title: Preselection of cases through expert clinical and radiological review significantly increases mutation detection rate in multiple epiphyseal dysplasia.
abstract: Skeletal dysplasias are difficult to diagnose for the nonexpert. In a previous study of patients with multiple epiphyseal dysplasia (MED), we identified cartilage oligomeric matrix protein (COMP) mutations in only 36% of cases and suspected that the low-mutation detection rate was partially due to misdiagnosis. We therefore instituted a clinical-radiographic review system, whereby all cases were evaluated by a panel of skeletal dysplasia experts (European Skeletal Dysplasia Network). Only those patients in whom the diagnosis of MED was confirmed by the panel were screened for mutations. Under this regimen the mutation detection rate increased to 81%. When clinical-radiological diagnostic criteria were relaxed the mutation rate dropped to 67%. We conclude that expert clinical-radiological review can significantly enhance mutation detection rates and should be part of any diagnostic mutation screening protocol for skeletal dysplasias.
authors.affiliation: Division of Molecular Paediatrics, Lausanne, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zankl
authors.forename: Gail C
authors.initials: GC
authors.lastname: Jackson
authors.forename: Laureane Mittaz
authors.initials: LM
authors.lastname: Crettol
authors.forename: Jacky
authors.initials: J
authors.lastname: Taylor
authors.forename: Rob
authors.initials: R
authors.lastname: Elles
authors.forename: Geert R
authors.initials: GR
authors.lastname: Mortier
authors.forename: Jurgen
authors.initials: J
authors.lastname: Spranger
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zabel
authors.forename: Sheila
authors.initials: S
authors.lastname: Unger
authors.forename: Martine Le
authors.initials: ML
authors.lastname: Merrer
authors.forename: Valerie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hall
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wright
authors.forename: Luisa
authors.initials: L
authors.lastname: Bonafe
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: Michael D
authors.initials: MD
authors.lastname: Briggs
mesh_terms: D000328:Adult; D064236:Cartilage Oligomeric Matrix Protein; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D008875:Middle Aged; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D011859:Radiography
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human