CHST3 was first reported in relation to autosomal recessive chondrodysplasia with congenital joint dislocations (SEDCJD) in 2004 (Thiele et al. 2004, PMID: 15215498). SEDCJD, also known as CHST3-related skeletal dysplasia is a rare bone disorder characterized by short stature of prenatal onset; dislocation of the knees, hips or elbows; club feet; limitation of range of motion of large joints; progressive kyphosis; and occasional scoliosis. Intellect, vision and hearing are normal. A total of thirteen unique variants (missense, nonsense, frameshift, indel) that have been reported in eleven probands in five publications (PMIDs: 15215498, 18513679, 29453417, 36729370, 37876363) are included in this curation. Variants in this gene segregated in eight additional family members (PMID: 15215498, 37876363). More genetic evidence is available in the literature, however, the maximum score (12pts) has been reached. The mechanism of pathogenicity is predicted to be loss-of-function. This gene-disease relationship is also supported by functional alteration studies in patient cells (PMID: 18513679). In summary, there is definitive evidence supporting the relationship between CHST3 and autosomal recessive chondrodysplasia with congenital joint dislocations. 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 ClinGen Skeletal Disorders GCEP on the meeting date August 4th, 2025 (SOP Version 11).
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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