COMP has been described in association with autosomal dominant Pseudoachondroplasia (PSACH), a form of short-limbed dwarfism characterized by marked short stature and deformity of the legs, short fingers, loose joints, and ligamentous laxity (Briggs et al. 1995). Radiographs of patients with PSACH often show small and irregular epiphyses, irregular metaphyses, and a delay in the ossification of annular epiphyses of the vertebrae (vertebral beaking) (Beighton and McKusick et al. 1993). Notably, COMP has also been associated with Multiple epiphyseal dysplasia (MED) which represents the mild end of this disease spectrum. This gene-disease relationship has been assessed separately by the ClinGen Skeletal Disorders Expert Panel and was found to have a definitive association. Monoallelic mutations are necessary and sufficient to cause both PSACH and MED phenotypes. Numerous unique variants in COMP have been identified in patients with PSACH (PMIDs: 29899997, 21644213, 21922596, 8307577, 27330822, 9388247). Case-level, segregation, and experimental evidence including a mouse model support this gene-disease relationship. In summary, COMP is definitively associated with autosomal dominant Pseudoachondroplasia. 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 2/7/2020. 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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