COMP has been described in association with autosomal dominant Multiple epiphyseal dysplasia (MED), a form of short-limb dwarfism characterized by short stature and early-onset osteoarthrosis (Briggs et al. 1995). Radiograph of patients with MED often show abnormalities of the epiphyseal centers in the knees, hands, shoulders and hips. Notably, COMP has also been associated with Pseudoachondroplasia (PSACH), which represents the severe end of the disease spectrum and is characterized by marked short stature, deformity of the legs, and ligamentous laxity (Briggs et al. 2001). The Skeletal Disorders Gene Curation Expert Panel has also evaluated the gene-disease relationship between COMP and PSACH and it was found to have a definitive association. Monoallelic mutations are necessary and sufficient to cause both PSACH and MED phenotypes. At least 10 unique missense variants in COMP have been identified in patients with MED (PMIDs: 21922596, 12483304, 17133256, 26920793, 21965141, 11565064, 15756302). Evidence supporting this gene-disease relationship includes case-level, segregation, and experimental data. In summary, COMP is definitively associated with autosomal dominant Multiple epiphyseal dysplasia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the Skeletal Disorders Gene Curation Expert Panel on 3/24/2020. Gene Clinical Validity Standard Operating Procedures (SOP) - Version 7.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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