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This summary reviews the association between the CER1 gene (HGNC:1862) and osteoporosis (MONDO_0005298). Two independent case‑control studies have provided strong evidence supporting the role of CER1 variations in contributing to low bone mineral density and increased fracture risk in postmenopausal women (PMID:22543871) (PMID:24138842). The clinical findings are reproducible across different cohorts, indicating a robust link between the genotype and the clinical phenotype. The synthesis of these data supports the clinical validity of using CER1 as a marker in diagnostic decision‑making. This overview is intended to aid commercial applications and provide a basis for future publications. In addition, the integrated evidence allows for further research to expand these initial findings.
The overall clinical validity of the CER1‑osteoporosis association has been classified as Strong. In the first study, a cohort of 300 postmenopausal women was evaluated, and significant associations with fracture risk and bone mineral density were reported (PMID:22543871). The second study, involving 607 women, confirmed these associations along with evidence for an impact on bone turnover markers and early menopause (PMID:24138842). Although there is no robust familial segregation data available (affected relatives: 0), the consistency of the case‑control findings weighs heavily in favor of a strong disease association. Both studies have advanced the understanding of how CER1 variations may contribute to osteoporosis risk. This strengthens the argument for its clinical relevance and potential use in genetic testing.
Analysis of the genetic evidence reveals that the disease association follows an autosomal dominant inheritance pattern. A representative variant, c.194C>G (p.Ala65Gly), meets the required criteria with a complete coding change, demonstrating both the nucleotide and protein-level alteration. Several other polymorphisms were investigated in these studies, with at least five demonstrating statistical significance. This variant category includes missense and intronic changes that may affect gene expression or protein function. The variant data emphasize a recurring theme of CER1 involvement in bone metabolism. Overall, the number and consistency of variants across separate cohorts support a strong genetic contribution.
While the evaluated segregation data show no additional affected relatives beyond the case–control cohorts, the reported variant spectrum remains informative. Both studies identified a mix of coding and non‑coding variations, underlining the complexity of CER1’s role in bone mineral density regulation. The diversity of the variant types—from missense variants like c.194C>G (p.Ala65Gly) to intronic changes—suggests multiple potential mechanisms for dysfunction. Although the absence of classic segregation data limits the familial component of the analysis, the cumulative genetic evidence confirms a significant association. This spectrum illustrates both the breadth and depth of CER1 alterations observed in osteoporotic populations. It also reinforces the need for further functional studies.
Functional evidence regarding the mechanism of pathogenicity for CER1 is currently limited. No direct functional assays or animal models were provided in the available studies, and the hypothesis of disrupted CER1 protein function is inferred from genetic correlations. The absence of tailored in vitro or in vivo functional assessment means that the mechanistic underpinning remains to be fully elucidated. However, the clinical correlations suggest that even subtle changes in CER1 activity could influence bone remodeling and mineral density. This gap in experimental data underscores the need for additional research to directly interrogate the functional impact of CER1 variants. Nevertheless, the clinical significance is well established by the genetic association data.
In summary, the available evidence establishes a strong link between CER1 variations and osteoporosis risk through two rigorously conducted case‑control studies. The genetic data, represented by variants such as c.194C>G (p.Ala65Gly), together with consistent clinical correlations, provide a compelling narrative for the gene‑disease association. Despite limited functional studies, the overall findings support the clinical application of CER1 testing for predicting osteoporosis and potentially guiding patient management. Key take‑home: CER1 genetic testing offers actionable insights for assessing osteoporotic fracture risk in postmenopausal women.
Gene–Disease AssociationStrongTwo independent case‑control studies, one with 300 postmenopausal women (PMID:22543871) and another with 607 women (PMID:24138842), provide robust evidence supporting the association. Genetic EvidenceStrongGenetic analyses identified multiple CER1 variants, including the representative c.194C>G (p.Ala65Gly), which consistently correlate with decreased bone mineral density and increased fracture risk in separate cohorts. Functional EvidenceLimitedNo direct functional studies have been reported, and the proposed mechanisms of pathogenicity are inferred from genetic correlations rather than demonstrated by experimental assays. |