Preselection of cases through expert clinical and radiological review significantly increases mutation detection rate in multiple epiphyseal dysplasia.
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.
Zankl
Andreas
A
Division of Molecular Paediatrics, Lausanne, Switzerland.
Jackson
Gail C
GC
Crettol
Laureane Mittaz
LM
Taylor
Jacky
J
Elles
Rob
R
Mortier
Geert R
GR
Spranger
Jurgen
J
Zabel
Bernhard
B
Unger
Sheila
S
Merrer
Martine Le
ML
Cormier-Daire
Valerie
V
Hall
Christine M
CM
Wright
Michael J
MJ
Bonafe
Luisa
L
Superti-Furga
Andrea
A
Briggs
Michael D
MD
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
D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human