Gene/phenotype/disorder under study
SMARCA4, Coffin-Siris syndrome, ID and cancer risk (OMIM # 603254)
Abstract
Missense variants in SMARCA4 can cause Coffin-Siris syndrome, usually —but not invariably— presenting with a specific BAFopathy DNA methylation episignature in blood. In contrast, germline truncating variants in SMARCA4 are associated with a predisposition to small-cell carcinoma of the ovary hypercalcemic type (SCCOHT) in young females. However, CSS phenotypes have also been observed in individuals harboring truncating SMARCA4 variants, underscoring the complexity of genotype–phenotype correlations and limiting the predictive value of variant type alone. This ambiguity is particularly challenging in the prenatal diagnostic context. We are therefore collecting cases with SMARCA4 variants (VUS, LP, P) to further delineate the associated phenotype.
Coordinating clinicians
Gijs Santen en Eline van der Sluijs – sluijs@lumc.nl
Institution
Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: Yes/No (depending on the variant)
2- Resampling of patients: No
3- Linked to a translational/basic research project: No