DCHS1 was first reported in relation to autosomal dominant congenital heart disease in 2023 (Zhou et al., PMID: 37399314). One variant (a missense) that has been reported in one proband in one publication (PMID: 37399314) is included in this curation. However, this variant was not scored as it is too frequent and it is not clear if the phenotype was present from birth. This gene-disease relationship is supported by animal models and expression studies. Lack of DCHS1 disrupts actin cytoskeleton in cardiac fibroblasts (PMID 35200715). Expression studies confirmed that DCHS1 is expressed early in human, chick and mouse development (PMIDs 35200715, 37147909). Mouse models demonstrated that deficiency of DCHS1 led to atrial septal defects and abnormal valve formation (PMIDs 35200715, 21303848). A zebrafish model demonstrated rescue of a heart failure phenotype with wildtype DCHS1 mRNA after depletion with morpholino (PMID 26258302). In summary, the evidence supporting the relationship between DCHS1 and autosomal dominant congenital heart disease has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role DCHS1 plays in this disease. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date 4/2/2024 (SOP Version 10).
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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