Alexander Burger1, Jasmien Roosenboom2, Mohammad Hossain3, Seth M Weinberg2,4,5, Jacqueline T Hecht1,3, Karen L Posey3. 1. Center for Craniofacial Research, UTHealth School of Dentistry, Houston, TX, USA. 2. Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA. 3. Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. 4. Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA. 5. Department of Anthropology, University of Pittsburgh, Pittsburgh, PA, USA.
Abstract
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.
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.
Authors: Francoise Coustry; Karen L Posey; Tristan Maerz; Kevin Baker; Annie M Abraham; Catherine G Ambrose; Sabah Nobakhti; Sandra J Shefelbine; Xiaohong Bi; Michael Newton; Karissa Gawronski; Lindsay Remer; Alka C Veerisetty; Mohammad G Hossain; Frankie Chiu; Jacqueline T Hecht Journal: Matrix Biol Date: 2018-01-05 Impact factor: 11.583
Authors: Alexander Burger; Jasmien Roosenboom; Mohammad Hossain; Seth M Weinberg; Jacqueline T Hecht; Karen L Posey Journal: Mol Genet Genomic Med Date: 2020-04-28 Impact factor: 2.473