DHCR24 was first reported in relation to autosomal recessive desmosterolosis in 2001 (Waterham et al., PMID: 11519011). This condition can include developmental delay, intellectual disability, brain abnormalities including decreased white matter, agenesis of the corpus callosum, and seizures. There may also be dysmorphic facial features, heart defects, and limb abnormalities. Prenatal features of this condition may include cystic hygroma, skin edema, ventriculomegaly, and joint contractures. Nine unique variants (missense, nonsense, canonical splice site) that have been reported in six probands in five publications (PMIDs: 11519011, 21559050, 21671375, 33027564, 38239854) are included in this curation. The mechanism of pathogenicity is reported to be loss of function. This gene-disease relationship is also supported by animal models, expression studies, and functional alteration studies (PMIDs: 21845517, 30891795, 25637936). Null mouse models recapitulate the rhizomelic limb shortening that has been observed in humans. Abnormal neuronal morphology has also been observed in null mouse models. In summary, there is definitive evidence supporting the relationship between DHCR24 and autosomal recessive desmosterolosis. 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 Prenatal GCEP on June 25, 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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