COL9A2 was first reported in relation to autosomal recessive Stickler syndrome in 2011 (Baker et al., PMID 21671392). At least 1 variant (frameshift) has been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, experimental data. Variants in this gene have been reported in at least 1 proband with Stickler syndrome in 1 publication (PMID 21671392). Variants in this gene segregated with disease in 1 additional family member. The mechanism for disease is biallelic loss of function causes the recessive, syndromic form, wheras heterozygous variants have been identified in patients with autosomal dominant epiphyseal dysplasia phenotype. This gene-disease association is supported by several expression studies investigating the collagen IX pathway in cartilage as well as several animal models with Col IX knockout generated by the disruption of Col9a1. Additionally, a canine model supports this association (Suzuki 2005, Goldstein 2010). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in inheritance pattern and phenotypic variability. Therefore, we have split curations for the disease entities, epiphyseal dysplasia. This classification was approved by the ClinGen Hearing Loss Working Group on 2/19/2019 (SOP Version 5).
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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