Mutant COMP shapes growth and development of skull and facial structures in mice and humans

BACKGROUND: Cartilage oligomeric matrix protein (COMP) is an important extracellular matrix protein primarily functioning in the musculoskeletal tissues and especially endochondral bone growth. Mutations in COMP cause the skeletal dysplasia pseudoachondroplasia (PSACH) that is characterized by short limbs and fingers, joint laxity, and abnormalities but a striking lack of skull and facial abnormalities. METHODS: This study examined both mice and humans to determine how mutant‐COMP affects face and skull growth. RESULTS: Mutant COMP (MT‐COMP) mice were phenotypically distinct. Snout length and skull height were diminished in MT‐COMP mouse and the face more closely resembled younger controls. Three‐dimensional facial measurements of PSACH faces showed widely spaced eyes, reduced lower facial height, and decreased nasal protrusion, which correlated with a more juvenile appearing face. Neither MT‐COMP mice nor PSACH individuals show midface hypoplasia usually associated with abnormal endochondral bone growth. MT‐COMP mice do show delayed endochondral and membranous skull ossification that normalizes with age. CONCLUSION: Therefore, mutant‐COMP affects both endochondral and intramembranous bones of the skull resulting in a reduction of the nose and lower facial height in mice and humans, in addition to its well‐defined role in the growth plate chondrocytes.